bvg Repression of Alcaligin Synthesis in Bordetella bronchiseptica Is Associated with Phylogenetic Lineage

Size: px
Start display at page:

Download "bvg Repression of Alcaligin Synthesis in Bordetella bronchiseptica Is Associated with Phylogenetic Lineage"

Transcription

1 JOURNAL OF BACTERIOLOGY, Nov. 1995, p Vol. 177, No /95/$ Copyright 1995, American Society for Microbiology bvg Repression of Alcaligin Synthesis in Bordetella bronchiseptica Is Associated with Phylogenetic Lineage PETER C. GIARDINA, 1,2 * LISA-ANNE FOSTER, 2 JAMES M. MUSSER, 3 BRIAN J. AKERLEY, 4 JEFF F. MILLER, 4 AND DAVID W. DYER 1 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 1 ; Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, New York 2 ; Section of Molecular Pathobiology, Department of Pathology, Baylor College of Medicine, Houston, Texas 3 ; and Department of Microbiology and Immunology, University of California School of Medicine, Los Angeles, California 4 Received 23 May 1995/Accepted 15 August 1995 Recent studies have shown that Bordetella bronchiseptica utilizes a siderophore-mediated transport system for acquisition of iron from the host iron-binding proteins lactoferrin and transferrin. We recently identified the B. bronchiseptica siderophore as alcaligin, which is also produced by B. pertussis. Alcaligin production by B. bronchiseptica is repressed by exogenous iron, a phenotype of other microbes that produce siderophores. In this study, we report that alcaligin production by B. bronchiseptica RB50 and GP1SN was repressed by the Bordetella global virulence regulator, bvg, in addition to being Fe repressed. Modulation of bvg locus expression with 50 mm MgSO 4 or inactivation of bvg by deletion allowed strain RB50 to produce alcaligin. In modulated organisms, siderophore production remained Fe repressed. These observations contrasted with our previous data indicating that alcaligin production by B. bronchiseptica MBORD846 and B. pertussis was repressed by Fe but bvg independent. Despite bvg repression of alcaligin production, strain RB50 was still able to acquire Fe from purified alcaligin, suggesting that expression of the bacterial alcaligin receptor was not repressed by bvg. We tested 114 B. bronchiseptica strains and found that bvg repression of alcaligin production was strongly associated with Bordetella phylogenetic lineage and with host species from which the organisms were isolated. Bordetella bronchiseptica is a gram-negative coccobacillus that colonizes the upper respiratory tract of several mammals (19). Colonization may lead to upper respiratory tract disease such as atrophic rhinitis in swine, an illness characterized by nasal turbinate atrophy, snout disfiguration, and weight loss (33, 40). In some cases, death results from pneumonia caused by secondary bacterial infections. B. bronchiseptica also predisposes swine to subsequent infection by Pasteurella multocida, which can severely exacerbate atrophic rhinitis (9 11). B. bronchiseptica causes infectious canine tracheobronchitis (kennel cough) in dogs (41, 50) and respiratory infections in other domesticated mammals (8, 19). Humans can sustain respiratory and other infections caused by B. bronchiseptica; these infections most commonly occur in immunocompromised individuals (15, 34, 48, 49). Our laboratory has been interested in examining how Fe transport by B. bronchiseptica contributes to pathogenesis. In order to successfully colonize a mammalian host, a pathogen must be able to obtain Fe, an essential cofactor in many biological oxidation-reduction reactions (43, 44). Although Fe is an essential nutrient for growth of virtually all microorganisms, the concentration of free Fe in the mammalian body is normally too low to support microbial growth (44). In mammals, most Fe is sequestered intracellularly. Extracellular Fe is bound to lactoferrin (LF; in exocrine secretions) or transferrin * Corresponding author. Mailing address: Oklahoma University Health Sciences Center, Department of Microbiology and Immunology, P.O. Box 73190, Oklahoma City, OK Phone: (405) Fax: (405) Electronic mail address: pgiardin@zena. uokhsc.edu. Present address: Department of Molecular Microbiology and Immunology, Washington University, St. Louis, MO (in plasma and tissue fluids) (44). This iron sequestration effectively limits Fe availability to most invading microorganisms and suppresses growth. This phenomenon has been termed nutritional immunity (43). To obtain essential Fe, many pathogenic bacteria have evolved the ability to synthesize and secrete small Fe-binding compounds, termed siderophores, that sequester Fe for use by the bacterial cell (32). Many studies have demonstrated that siderophore-mediated iron transport is critical in supporting pathogenesis. For example, the ability of enteroinvasive Escherichia coli to synthesize and secrete aerobactin correlates directly with the ability of these organisms to cause disease (47). B. bronchiseptica secretes an Fe-chelating compound, alcaligin (28), that is able to remove Fe from LF and transferrin (1, 6, 17, 20). The metabolic pathway for alcaligin biosynthesis and secretion, and the uptake mechanism for the Fe chelate, are not understood. However, it is clear that, similar to the control of siderophore synthesis by other bacteria, alcaligin production is regulated by Fe availability (17). That is, when B. bronchiseptica is Fe starved, the organism produces alcaligin. Release of this siderophore is not detected when the organism is grown in Fe-replete conditions. Studies from our laboratory and others previously suggested that Bordetella alcaligin production was independent of bvg control (20). The bvg operon (36), encoding a complex twocomponent regulator (42), controls the expression of many Bordetella virulence determinants. This operon includes BvgS, a transmembrane sensory protein, and BvgA, a cytoplasmic, transcriptional activator of several Bordetella virulence determinants, including filamentous hemagglutinin (35), fimbriae (46), adenylate cyclase toxin (18), and dermonecrotic toxin (25). BvgA also regulates its own expression (36, 37) and the synthesis of certain outer membrane proteins of unknown 6058

2 VOL. 177, 1995 REGULATION OF ALCALIGIN PRODUCTION 6059 TABLE 1. Bacterial strains and plasmids used Strain or plasmid Description Reference Bordetella strains MBORD846 bvg pig isolate 1 MBA4 MBORD846 bvgs 54 This study RB50 bvg rabbit isolate 12 RBA2 RB50 frlab 2 RB53 RB50 bvgs-c3; bvg(con) 12 RB54 bvgas derivative of RB50 12 RBA1 RB54 frlab 2 GP1SN bvg guinea pig isolate 4 DM107 GP1SN bvgas 4 Plasmids pba291 prk415 containing frlab 2 prk415 Cloning vector function (16, 45). The present report demonstrates that in certain strains of B. bronchiseptica, alcaligin production is repressed by bvg. We further discovered that bvg repression of alcaligin synthesis strongly correlated with phylogenetic lineage as defined by multilocus enzyme electrophoresis (MLEE) analysis (30, 31) and with the host species from which a particular B. bronchiseptica strain was isolated. MATERIALS AND METHODS Bacteria, plasmids, and media. B. bronchiseptica strains and plasmids used in the initial phase of this study are described in Table 1. All strains were routinely cultured on Bordet-Gengou (BG) agar base (Difco Laboratories, Detroit, Mich.) containing 15% defibrinated sheep blood (Crane Laboratories, Syracuse, N.Y.). Chelex-treated Stainer-Scholte medium (CSSM) and Chelex-treated defined medium (CDM) in which N-2-hydroxyethylpiperazine-N -2-ethanesulfonic acid (HEPES) buffer was substituted with Tris buffer (ph 7.4) were prepared as previously described (1, 17, 39). All experiments involving LF were carried out in CDM supplemented with 10 mm sodium bicarbonate. Bovine LF (Sigma Chemical Co., St. Louis, Mo.) was prepared as previously described (1, 17). Ferrous sulfate was prepared daily and used as a supplemental Fe source at a final concentration of 10 M, where indicated. Ferric nitrate (ph 4.0) was used at a final concentration of 10 M. Purified desferri-alcaligin was kindly provided by Chris Moore and Bradley Gibson (University of California, San Francisco) (28). When indicated, media were supplemented with 50 mm MgSO 4 to modulate the expression of bvg-dependent virulence determinants. All glassware was washed in 3 N nitric acid and rinsed with 10 changes of deionized distilled water as previously described (1, 17); alternatively, tissue culture-grade, sterile plasticware was used to eliminate Fe contamination. Growth conditions. For all growth assays, B. bronchiseptica strains were cultured on BG blood agar for 48 h at 37 C. The organisms were transferred to 10 ml of fresh growth medium (CSSM or CDM) with a Dacron swab (Baxter Scientific Products, McGaw Park, Ill.) and incubated overnight at 37 C with rotary shaking at 250 rpm. The organisms were sedimented by centrifugation, washed with a 10-ml volume of fresh medium, and suspended in fresh medium. The optical density was adjusted to 10 to 20 Klett units, using a Klett-Summerson colorimeter (green filter), or to 0.05 to 0.07 U at 660 nm in a Spectronic 21D spectrophotometer (Milton Roy Company). An Fe source was added, incubation was continued at 37 C with rotary shaking, and growth was periodically assessed by optical density measurement. A sample from each culture was transferred to BG blood agar to determine the presence of bvg phase variants. To determine if a culture produced alcaligin, the cells were sedimented by centrifugation, and the culture supernatants were filter sterilized. All culture supernatants were then assayed for the presence of alcaligin with the Csaky assay as previously described (1, 14). To determine the effect of phenotypic modulation of bvg on alcaligin synthesis, cells were grown for 48 h on BG blood agar supplemented with 50 mm MgSO 4. Organisms from nonhemolytic colonies were cultured as described above except that the growth medium was supplemented with 50 mm MgSO 4. Following the experiment, bacteria were again cultured on BG blood agar without MgSO 4,to confirm that nonhemolytic organisms were phenotypically modulated and not phase variants that had sustained a genetic mutation in the bvg operon. RB53, a bvg(con) mutant of RB50 in which the modulation of bvg is prevented by a point mutation in bvgs, was used as a negative control (12, 27). Survey of strains for alcaligin production. Raised, hemolytic colonies (bvg ) were transferred to CSSM and incubated at 37 C in a rotary shaker for 20 h. Cells were sedimented by centrifugation, and the supernatants were analyzed in duplicate for the presence of alcaligin with the Csaky assay (14). Experiments were performed twice each in the presence and absence of 50 mm MgSO 4. In certain instances, strains that did not produce detectable alcaligin after 20 h of culture were incubated for an additional 24 to 28 h prior to collection of culture supernatants for the Csaky assay. Strains that did not produce detectable hydroxamate under these conditions were also examined by using the more sensitive chrome azurol S assay (38). RESULTS Strain-dependent repression of alcaligin production by bvg. Our previous work showed that alcaligin production by B. bronchiseptica MBORD846 was repressed when the organism was grown in the presence of as little as 10 M Fe. Moreover, alcaligin production was not controlled by the bvg operon (17). Similar results have been noted by other authors (20). The availability of defined mutants in the B. bronchiseptica bvg operon (3, 12) led us to reexamine this issue, in order to confirm that alcaligin production was independent of bvg regulation. Surprisingly, B. bronchiseptica RB50 did not secrete detectable alcaligin in the nonmodulated (Bvg ) state, even when Fe starved (Table 2). However, when RB50 was phenotypically modulated by growth with 50 mm MgSO 4 in CSSM, the organism produced copious amounts ( 50 M) of alcaligin in response to Fe stress (Table 2). Fe-starved RB50 grew to comparable extents (as measured by optical density), whether or not the organism was modulated (data not shown). Thus, excretion of alcaligin by modulated RB50 was not due to a nonspecific effect on the growth of the organism. Strain RB54, lacking a functional bvg locus (bvg), produced alcaligin in response to Fe stress (Table 2), irrespective of the presence of MgSO 4. Strain RB53, which is constitutively bvg and does not respond to modulating signals (12, 28), did not secrete alcaligin under any tested conditions, including Fe starvation in the presence of 50 mm MgSO 4. We also tested a second isogenic pair of B. bronchiseptica strains, GP1SN (bvg ) and DM107, a bvgas deletion mutant of GP1SN (bvg) (4). GP1SN and DM107 behaved similarly to RB50 and RB54. That is, the wild-type strain (GP1SN) did not produce alcaligin, while the bvg derivative (DM107) produced alcaligin in an Fe-repressible manner (data not shown). These data were in contrast to earlier reports indicating that alcaligin production was independent of bvg, including our observations on B. bronchiseptica MBORD846 (20). Modulation of strain MBORD846 with 50 mm MgSO 4 did not alter the amount of alcaligin produced compared with cells grown under nonmodulating conditions. To confirm that alcaligin production by strain MBORD846 was independent of bvg, we constructed a bvg deletion derivative of this strain, designated MBA4, as previously described (3, 12). Strain MBA4 produced alcaligin at levels comparable to those produced by MBORD 846, indicating that a deletion of the bvg locus did not enhance alcaligin production in this strain (data not shown). Alcaligin synthesis remained responsive to Fe stress. These observations suggested that in some strains of B. bronchiseptica (such as RB50), alcaligin production was under dual control by bvg and Strain (genotype) TABLE 2. Alcaligin production is repressed by bvg Alcaligin production MgSO 4 MgSO 4 Fe Fe Fe Fe RB50 (bvg ) RB53 [bvg(con)] RB54 (bvg)

3 6060 GIARDINA ET AL. J. BACTERIOL. FIG. 1. RB50 used LF as an iron source when purified desferri-alcaligin is added:, LF added; å, LF and purified desferri-alcaligin added. (A) Strain RB50; (B) strain RB54. Fe repression, while in other strains (such as MBORD846), alcaligin synthesis was susceptible only to Fe repression. Strain RB50 can use purified alcaligin for growth with LF. In general, siderophore receptor expression in bacteria is regulated by the same mechanisms that regulate siderophore production (22). If this is also true for B. bronchiseptica, then expression of the alcaligin receptor by RB50 should be repressed by bvg. Therefore, we cultured B. bronchiseptica RB50 with bovine LF and determined whether purified alcaligin could mediate transfer of Fe from LF to the organism. The results are shown in Fig. 1. B. bronchiseptica RB50 (Bvg, not modulated) did not grow in the presence of bovine LF (Fig. 1). In contrast, strain RB54 grew easily in CDM containing LF (Fig. 1). When we added purified desferri-alcaligin to these cultures, strain RB50 grew with bovine LF, while growth of RB54 with LF was slightly enhanced (Fig. 1). Therefore, RB50 was capable of growth with LF if exogenous alcaligin was provided to the organism. These data suggested that although alcaligin production in strain RB50 was repressed by the bvg locus, the ability to metabolize ferri-alcaligin complexes was not repressed by bvg. Alcaligin synthesis is not controlled by frl. Akerley et al. have shown that motility in strain RB50 is inhibited by bvg through repression of frl, a positive regulator of the fla operon (2, 3). Because control of alcaligin production in strain RB50 is phenotypically similar to control of motility (both are repressed by bvg), bvg-mediated repression of motility may act through the action of bvg on frl. We therefore examined if alcaligin production was affected by frl mutations that block activation of motility. These experiments were done under nonmodulating conditions. The results are shown in Table 3. While RBA2 (bvg frl) did not make alcaligin when Fe stressed, strain RBA1 (bvg frl) produced alcaligin in normal amounts, and siderophore synthesis was derepressed by Fe limitation. Introduction of a plasmid-borne copy of frl (pba291) into RBA1 had no effect on alcaligin production (Table 3). These results indicated that alcaligin production was not dependent on the frl transactivator and that bvg repression of alcaligin production was not mediated through an effect on frl. Phylogeny of bvg repression of alcaligin production. Is the phenotypic repression of alcaligin production in strains RB50 and GP1SN unusual, or does strain MBORD846 represent a laboratory artifact that has spontaneously lost bvg repression of alcaligin synthesis? Musser et al. (30, 31) identified 21 distinct electrophoretic types (ETs) of B. bronchiseptica, marking phylogenetic lineages that were grouped into five MLEE clusters, A to E. We examined 114 of these strains for bvg repression of alcaligin synthesis and compared the observed phenotype with the lineage of each strain. A complete list of these strains, including the ET, host, country of origin, and relevant phenotype is available from D.W.D. ET1, ET1a, ET3, and ET4 represent clones from MLEE cluster A, clones ET6, ET6a, and ET8 are members of MLEE cluster B, and ET14 and ET16 are clones assigned to MLEE cluster D. Since MLEE clusters C and E were each represented by one phylogenetic lineage and together contained only three strains (31), they were not examined in this study. We identified two groups of strains based on the conditions under which alcaligin was produced. Group 1 strains (total of 46) resembled strain MBORD846 in that they produced alcaligin in response to Fe stress but independently of bvg. Strains in group 2 (total of 64), like strain RB50, were bvg repressed for alcaligin production. Supernatants from a minority of strains (total of four) were devoid of iron-binding activity in the chrome azurol S assay and did not appear to secrete siderophore under any tested conditions (data not shown). The association of bvg regulation of alcaligin production with MLEE cluster is shown in Table 4. The majority (75%) of strains in MLEE cluster A were in group 1 (bvg independent), while the majority of MLEE cluster B (88%) and D (100%) were in group 2 (bvg repressed). This relationship remained consistent when bvg regulation was compared with phylogenetic lineage (Table 5). Individual ETs from cluster A were TABLE 3. Alcaligin production is independent of frl Strain (genotype) Fe Alcaligin production Fe RB50 (bvg frl ) RB54 (bvg frl ) RBA2 (bvg frl) RBA1 (bvg frl) RBA1(pRK415) RBA1(pBA291)

4 VOL. 177, 1995 REGULATION OF ALCALIGIN PRODUCTION 6061 TABLE 4. bvg repression of alcaligin production is associated with phylogenetic cluster No. (%) of strains tested MLEE cluster within the cluster Group 1 Group 2 A 43 (75) 14 (25) B 2 (12) 15 (88) D 0 (0) 29 (100) predominantly in group 1, while ETs from clusters B and D were predominantly group 2. Equally striking was the association between the independence of alcaligin production from bvg repression with the ability of B. bronchiseptica to infect pigs (Table 6). Among the 30 tested pig strains, 94% (28 strains) were found to produce alcaligin in a bvg-independent manner (group 1). The majority of strains isolated from other hosts were in group 2 (bvg repressed). Taken together, these data indicated that the mode of regulation of alcaligin was strongly associated with phylogenetic lineage and with the host species from which each strain was obtained. DISCUSSION MLEE cluster TABLE 5. bvg repression of alcaligin is associated with B. bronchiseptica phylogenetic lineage ET No. (%) of total strains tested within the phylogenetic lineage Group 1 (bvg-independent) Group 2 (bvg-repressed) Total tested A 1 38 (74.5) 13 (25.5) 51 1a (100) B (89) 9 6a (86) 7 D (100) 28 ND a ND Total a ND, not determined. The bvg operon has been shown to directly or indirectly modify the expression of a variety of virulence determinants in B. bronchiseptica and B. pertussis in response to environmental signals. In this study, we have demonstrated that in certain strains of B. bronchiseptica, alcaligin biosynthesis is repressed by bvg as well as by Fe and that derepression of alcaligin synthesis can be achieved by genetic mutation of the bvg operon or by exposing the organisms to modulating conditions in culture. The rabbit isolate, RB50, failed to secrete alcaligin in iron-limited media unless phenotypically modulated by MgSO 4 (Table 2). Further, strain RB53, a bvg(con) mutant of RB50 that is unresponsive to modulating conditions, failed to produce alcaligin under any tested conditions. In the isogenic bvg deletion mutant, RB54, alcaligin production was iron repressible but independent of bvg. This eliminated the possibility that the Mg 2 ion may have spuriously interfered with repression of alcaligin synthesis by Fe rather than by bvg. Similar results were obtained for GP1SN, a guinea pig isolate (data not shown). These data conflicted with what we (17) and others (20) previously reported with regard to alcaligin production in Bordetella species. Little is known about the mode of bvg repression at the molecular level. Akerley et al. (4) demonstrated that motility in B. bronchiseptica RB50 is bvg repressed, which is phenotypically identical to regulation of alcaligin production in this strain. Although motility and alcaligin production were phenotypically regulated similarly in strain RB50, we found that frl was not involved in regulation of alcaligin biosynthesis (Table 3). Nonetheless, we cannot rule out the possibility that regulation of alcaligin is mediated through an activator similar to FrlAB. Interestingly, the ferri-alcaligin uptake system was expressed at some level when Fe stressed, even in the absence of modulating factors. When Fe stressed, RB50 was able to use purified alcaligin as an iron source in the absence of detectable alcaligin production (Fig. 1). This is unlike the regulation of most other siderophore uptake systems that are coordinately regulated with siderophore production. We surveyed 114 strains of B. bronchiseptica, previously defined by MLEE analysis (30, 31), for alcaligin production under various conditions. Among these strains, we found two distinct groups that differed in whether alcaligin synthesis was bvg repressed. These data suggested a relationship between phylogenetic lineage, mammalian host species, and mode of regulation of alcaligin production. Musser and coworkers earlier demonstrated a relationship between B. bronchiseptica phylogenetic lineage and the mammalian hosts from which these organisms were isolated (30, 31). For example, ET1 strains, which we showed to be predominantly bvg independent for alcaligin production, preferentially infect pigs as opposed to other hosts. Therefore, the events that occurred during the differentiation of the ET1 phylogenetic lineage may have included a mutation that rendered alcaligin synthesis independent of bvg. Akerley et al. have recently suggested that bvg repression is important for suppressing the expression of determinants that would otherwise interfere with colonization by B. bronchiseptica (2). This suggests that alcaligin production may be essential for B. bronchiseptica colonization of pigs but perhaps not critical in other hosts. Further, the combined population genetic data suggest that the Bordetella species capable of infecting mammals (B. bronchiseptica, B. pertussis, and B. parapertussis) are actually biovars of a single genetic species (23, 29 31). Thus, differences in expression of alcaligin production in B. bronchiseptica isolates from different phylogenetic lineages are similar to variation in the expression of other virulence determinants between these three species. For example, B. pertussis and B. parapertussis Host TABLE 6. bvg repression of alcaligin is associated with mammalian host species Predominant phenotype a % of total (no. of strains within the predominant phenotype/total no. tested) Pig Group 1 94 (28/30) Cat Group 2 90 (9/10) Dog Group 2 80 (20/25) Guinea pig Group 2 82 (9/11) Horse Group 2 86 (6/7) Koala Group (3/3) Rabbit Group 2 59 (10/17) a Group 1, alcaligin production is bvg independent; group 2, alcaligin production is bvg repressed.

5 6062 GIARDINA ET AL. J. BACTERIOL. harbor the fla operon found in B. bronchiseptica strains, although the former organisms are not motile under any conditions (24). Beattie et al. have shown that the vrg-6 locus is essential for B. pertussis virulence in a murine model (7). Although vrg-6 is not expressed in B. bronchiseptica, the latter organism harbors a silent copy of this locus (7). Most strikingly, B. parapertussis and B. bronchiseptica have intact genes for the pertussis toxin (ptx) operon (5, 21, 26), although only B. pertussis secretes the toxin. In B. parapertussis and B. bronchiseptica, the ptx operon is functionally silent due to promoter mutations (26). Also, single base substitutions found in the silent B. parapertussis locus were found in the silent B. bronchiseptica locus (26), suggesting that these changes took place in a common progenitor. B. bronchiseptica retains the complex secretion machinery necessary to transport the multicomponent toxin into the extracellular space (13, 26). Collectively, these data are consistent with the idea that the phylogenetic lineages of mammalian Bordetella species have only recently diverged from one another. As B. pertussis, B. parapertussis, and ET1 strains of B. bronchiseptica are highly host specific, the population genetic data further suggest that subtle allelic variation among the phylogenetic lineages of mammalian Bordetella species probably contribute significantly to host specificity. Our data suggest that release of bvg repression of alcaligin production by ET1 B. bronchiseptica strains may have been a significant event in the development of the ability of these strains to specifically colonize swine. Conversely, bvg repression of alcaligin synthesis may be important for maintaining colonization of other hosts. Since alcaligin synthesis by human Bordetella strains (i.e., B. pertussis strains) is similarly unresponsive to bvg repression (17), alcaligin production may also be critical for the colonization of the human respiratory tract. ACKNOWLEDGMENTS This work was supported by grant from the U.S. Department of Agriculture (D.W.D.) and by grant A from the National Institute of Allergy and Infectious Disease (J.E.M.). REFERENCES 1. Agiato, L. A., and D. W. Dyer Siderophore production and membrane protein alterations by Bordetella pertussis in response to iron starvation. Infect. Immun. 60: Akerley, B. J., P. A. Cotter, and J. F. Miller Ectopic expression of the flagellar regulon alters development of the Bordetella-host interaction. Cell 80: Akerley, B. J., and J. F. Miller Flagellin gene transcription in Bordetella bronchiseptica is regulated by the BvgAS virulence control system. J. Bacteriol. 175: Akerley, B. J., D. M. Monack, S. Falkow, and J. F. Miller The bvgas locus negatively controls motility and synthesis of flagella in Bordetella bronchiseptica. J. Bacteriol. 174: Aricò, B., and R. Rappuoli Bordetella parapertussis and Bordetella bronchiseptica contain transcriptionally silent pertussis toxin genes. J. Bacteriol. 169: Armstrong, S. K., and M. O. Clements Isolation and characterization of Bordetella bronchiseptica mutants deficient in siderophore activity. J. Bacteriol. 175: Beattie, D. T., R. Shahin, and J. J. Mekalanos A vir-repressed gene of Bordetella pertussis is required for virulence. Infect. Immun. 60: Bemis, D. A Bordetella and Mycoplasma respiratory infections in dogs and cats. Vet. Clin. North Am. 22: Chanter, N., T. Magyar, and J. M. Rutter Interactions between Bordetella bronchiseptica and toxigenic Pasteurella multocida in atrophic rhinitis of pigs. Res. Vet. Sci. 47: Chung, W.-B., M. T. Collins, and L. R. Backstrom Adherence of Bordetella bronchiseptica and Pasteurella multocida to swine nasal ciliated epithelial cells in vitro. Acta Pathol. Microbiol. Immunol. Scand. 98: Confer, A. W Immunogens of Pasteurella. Vet. Microbiol. 37: Cotter, P. A., and J. F. Miller BvgS-mediated signal transduction: analysis of phase-locked regulatory mutants of Bordetella bronchiseptica in a rabbit model. Infect. Immun. 62: Covacci, A., and R. Rappuoli Pertussis toxin export requires accessory genes located downstream from the pertussis toxin operon. Mol. Microbiol. 8: Csaky, T. Z On the estimation of bound hydroxylamine in biological materials. Acta Chem. Scand. 2: de la Fuente, J., C. Albo, A. Rodriguez, B. Sopena, and C. Martinez Bordetella bronchiseptica pneumonia in a patient with AIDS. Thorax 49: Finn, T. M., R. Shahin, and J. J. Mekalanos Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis. Infect. Immun. 59: Foster, L. A., and D. W. Dyer A siderophore production mutant of Bordetella bronchiseptica does not grow with lactoferrin as an iron source. Infect. Immun. 61: Glaser, P., D. Ladant, D. Sezer, A. Pichot, A. Ullmann, and A. Danchin The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in E. coli. Mol. Microbiol. 2: Goodnow, R. A Biology of Bordetella bronchiseptica. Microbiol. Rev. 44: Gorringe, A. R., G. Woods, and A. Robinson Growth and siderophore production by Bordetella pertussis under iron-restricted conditions. FEMS Microbiol. Lett. 66: Gross, R., B. Aricò, and R. Rappuoli Genetics of pertussis toxin. Mol. Microbiol. 3: Guerinot, M. L Microbial iron transport. Annu. Rev. Microbiol. 48: Kloos, W. E., N. Mohapatra, W. J. Dobrogosz, J. W. Ezzel, and C. R. Manclark Deoxyribonucleotide sequence relationships among Bordetella species. Int. J. Syst. Bacteriol. 31: Leigh, A. F., J. G. Coote, R. Parton, and C. J. Duggleby Chromosomal DNA from both flagellate and non-flagellate Bordetella species contains sequences homologous to the Salmonella H1 flagellin gene. FEMS Microbiol. Lett. 111: Livey, I., and A. C. Wardlaw Production and properties of Bordetella pertussis heat-labile toxin. J. Med. Microbiol. 17: Marchitto, K. S., S. G. Smith, C. Locht, and J. Keith Nucleotide sequence homology to pertussis toxin gene in Bordetella bronchiseptica and Bordetella parapertussis. Infect. Immun. 55: Miller, J. F., S. A. Johnson, W. J. Black, D. T. Beattie, J. J. Mekalanos, and S. Falkow Constitutive sensory transduction mutations in the Bordetella pertussis bvgs gene. J. Bacteriol. 174: Moore, C. H., L.-A. Foster, D. G. Gerbig, D. W. Dyer, and B. W. Gibson Identification of alcaligin as the siderophore produced by Bordetella pertussis and B. bronchiseptica. J. Bacteriol. 177: Müller, M., and A. Hildebrandt Nucleotide sequences of the 23S rrna genes from Bordetella pertussis, B. parapertussis, B. bronchiseptica and B. avium, and their implications for phylogenetic analysis. Nucleic Acids Res. 21: Musser, J. M., D. A. Bemis, H. Ishikawa, and R. K. Selander Clonal diversity and host distribution in Bordetella bronchiseptica. J. Bacteriol. 169: Musser, J. M., E. L. Hewlett, and M. S. Peppler Genetic diversity and relationships in populations of Bordetella spp. J. Bacteriol. 166: Neilands, J. B Microbial iron compounds. Annu. Rev. Biochem. 50: Pearce, H. G., and C. K. Roe Infectious porcine atrophic rhinitis: a review. Can. Vet. J. 7: Reina, J., A. Bassa, I. Llompart, N. Borrell, J. Gomez, and A. Serra Pneumonia caused by Bordetella bronchiseptica in a patient with a thoracic trauma. Infection 19: Relman, D. A., M. Domenighini, E. Tuomanen, R. Rappuoli, and S. Falko Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence. Proc. Natl. Acad. Sci. USA 86: Roy, C. R., J. F. Miller, and S. Falkow Autogenous regulation of the Bordetella pertussis bvgabc operon. Proc. Natl. Acad. Sci. USA 87: Scarlato, V., A. Prugnola, B. Aricó, and R. Rappuoli Post transcriptional feedback at the bvg locus controls expression of virulence factors in Bordetella pertussis. Proc. Natl. Acad. Sci. USA 87: Schwyn, B., and J. B. Neilands Universal chemical assay for the detection and determination of siderophores. Anal. Biochem. 160: Stainer, S., and M. Scholte A simple chemically defined medium for the production of phase I Bordetella pertussis. J. Gen. Microbiol. 63: Switzer, W. P Studies on infectious atrophic rhinitis. V. Concepts that several agents may cause turbinate atrophy. Am. J. Vet. Res. 17: Thompson, H., I. A. McCandlish, and N. G. Wright Experimental respiratory disease in dogs due to Bordetella bronchiseptica. Res. Vet. Sci. 20: Uhl, M. A., and J. F. Miller Autophosphorylation and phosphotransfer in the Bordetella pertussis BvgAS signal transduction system. Proc. Natl. Acad. Sci. USA 91: Weinberg, E. D Cellular iron metabolism in health and disease. Drug Metab. Rev. 22:

6 VOL. 177, 1995 REGULATION OF ALCALIGIN PRODUCTION Weinberg, E. D Iron and infection. Microbiol. Rev. 42: Weiss, A. A., A. R. Melton, K. E. Walker, C. Andraos-Selim, and J. J. Meidl Use of the promoter fusion transposon Tn5 lac to identify mutations in Bordetella pertussis vir-regulated genes. Infect. Immun. 57: Willems, R., A. Paul, H. G. van der Heide, A. R. ter Avest, and F. R. Mooi Fimbrial phase variation: a novel mechanism for transcriptional regulation. EMBO J. 9: Williams, P. H., and N. H. Carbonetti Iron, siderophores, and the pursuit of virulence: independence of the aerobactin and enterochelin iron uptake systems in Escherichia coli. Infect. Immun. 51: Winters, J. L., W. N. O connor, R. A. Broughton, and J. A. Noonan Bordetella bronchiseptica pneumonia in a patient with Down syndrome: a case report and review. Pediatrics 89: Woolfrey, B. F., and J. A. Moody Human infections associated with Bordetella bronchiseptica. Clin. Microbiol. Rev. 4: Wright, N. G., H. Thompson, D. Taylor, and H. J. C. Cornwell Bordetella bronchiseptica: a re-assessment of its role in canine respiratory disease. Vet. Rec. 93:

BvgAS Is Sufficient for Activation of the Bordetella pertussis ptx Locus in Escherichia coli

BvgAS Is Sufficient for Activation of the Bordetella pertussis ptx Locus in Escherichia coli JOURNAL OF BACTERIOLOGY, Nov. 1995, p. 6477 6485 Vol. 177, No. 22 0021-9193/95/$04.00 0 Copyright 1995, American Society for Microbiology BvgAS Is Sufficient for Activation of the Bordetella pertussis

More information

Regulatory Mutants of Bordetella bronchiseptica in a

Regulatory Mutants of Bordetella bronchiseptica in a INFCTION AND IMMUNITY, Aug. 1994, P. 3381-339 19-9567/94/$4.+ Copyright 3 1994, American Society for Microbiology Vol. 62, No. 8 BvgAS-Mediated Signal Transduction: Analysis of Phase-Locked Regulatory

More information

Restriction Endonuclease Analysis Discriminates Bordetella bronchiseptica Isolates

Restriction Endonuclease Analysis Discriminates Bordetella bronchiseptica Isolates JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2000, p. 4387 4393 Vol. 38, No. 12 0095-1137/00/$04.00 0 Restriction Endonuclease Analysis Discriminates Bordetella bronchiseptica Isolates RANDY E. SACCO,* KAREN

More information

Neither the Bvg Phase nor the vrg6 Locus of Bordetella pertussis Is Required for Respiratory Infection in Mice

Neither the Bvg Phase nor the vrg6 Locus of Bordetella pertussis Is Required for Respiratory Infection in Mice INFECTION AND IMMUNITY, June 1998, p. 2762 2768 Vol. 66, No. 6 0019-9567/98/$04.00 0 Copyright 1998, American Society for Microbiology Neither the Bvg Phase nor the vrg6 Locus of Bordetella pertussis Is

More information

Phenotypic modulation of the Bvg+ phase is not required for pathogenesis and. transmission of Bordetella bronchiseptica in swine

Phenotypic modulation of the Bvg+ phase is not required for pathogenesis and. transmission of Bordetella bronchiseptica in swine IAI Accepts, published online ahead of print on 12 December 2011 Infect. Immun. doi:10.1128/iai.06016-11 Copyright 2011, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights

More information

Investigation of the molecular biology and contribution to virulence of Bordetella bronchiseptica urease

Investigation of the molecular biology and contribution to virulence of Bordetella bronchiseptica urease University of Wollongong Research Online University of Wollongong Thesis Collection University of Wollongong Thesis Collections 1999 Investigation of the molecular biology and contribution to virulence

More information

Virulence of Bordetella bronchiseptica: Role of Adenylate Cyclase-Hemolysin

Virulence of Bordetella bronchiseptica: Role of Adenylate Cyclase-Hemolysin INFEcrION AND IMMUNITY, OCt. 1993, p. 472-478 Vol. 61, No. 1 19-9567/93/1472-7$2./ Copyright 1993, American Society for Microbiology Virulence of Bordetella bronchiseptica: Role of Adenylate Cyclase-Hemolysin

More information

Isolation and Characterization of Bordetella bronchiseptica Mutants Deficient in Siderophore Activity

Isolation and Characterization of Bordetella bronchiseptica Mutants Deficient in Siderophore Activity JOURNAL OF BACTERIOLOGY, Feb. 1993, p. 1144-1152 0021-9193/93/041144-09$02.00/0 Copyright X 1993, American Society for Microbiology Vol. 175, No. 4 Isolation and Characterization of Bordetella bronchiseptica

More information

The Bvg Virulence Control System Regulates Biofilm Formation in Bordetella bronchiseptica

The Bvg Virulence Control System Regulates Biofilm Formation in Bordetella bronchiseptica JOURNAL OF BACTERIOLOGY, Sept. 2004, p. 5692 5698 Vol. 186, No. 17 0021-9193/04/$08.00 0 DOI: 10.1128/JB.186.17.5692 5698.2004 Copyright 2004, American Society for Microbiology. All Rights Reserved. The

More information

Identification of a Locus Required for the Regulation of bvg- Repressed Genes in Bordetella pertussis

Identification of a Locus Required for the Regulation of bvg- Repressed Genes in Bordetella pertussis JOURNAL OF BACTERIOLOGY, May 1995, p. 2727 2736 Vol. 177, No. 10 0021-9193/95/$04.00 0 Copyright 1995, American Society for Microbiology Identification of a Locus Required for the Regulation of bvg- Repressed

More information

Role of Antibodies in Immunity to Bordetella Infections

Role of Antibodies in Immunity to Bordetella Infections INFECTION AND IMMUNITY, Apr. 2003, p. 1719 1724 Vol. 71, No. 4 0019-9567/03/$08.00 0 DOI: 10.1128/IAI.71.4.1719 1724.2003 Copyright 2003, American Society for Microbiology. All Rights Reserved. Role of

More information

Identification and Purification of Transferrin- and Lactoferrin- Binding Proteins of Bordetella pertussis and Bordetella bronchiseptica

Identification and Purification of Transferrin- and Lactoferrin- Binding Proteins of Bordetella pertussis and Bordetella bronchiseptica INFECTION ND IMMUNITY, Nov. 1991, p. 3982-3988 Vol. 59, No. 11 0019-9567/91/113982-07$02.00/0 Copyright 1991, merican Society for Microbiology Identification and Purification of Transferrin- and Lactoferrin-

More information

Mechanisms and Pathways of AMR in the environment

Mechanisms and Pathways of AMR in the environment FMM/RAS/298: Strengthening capacities, policies and national action plans on prudent and responsible use of antimicrobials in fisheries Final Workshop in cooperation with AVA Singapore and INFOFISH 12-14

More information

Filamentous Hemagglutinin of Bordetella bronchiseptica Is Required for Efficient Establishment of Tracheal Colonization

Filamentous Hemagglutinin of Bordetella bronchiseptica Is Required for Efficient Establishment of Tracheal Colonization INFECTION AND IMMUNITY, Dec. 1998, p. 5921 5929 Vol. 66, No. 12 0019-9567/98/$04.00 0 Copyright 1998, American Society for Microbiology. All Rights Reserved. Filamentous Hemagglutinin of Bordetella bronchiseptica

More information

Consequences of Antimicrobial Resistant Bacteria. Antimicrobial Resistance. Molecular Genetics of Antimicrobial Resistance. Topics to be Covered

Consequences of Antimicrobial Resistant Bacteria. Antimicrobial Resistance. Molecular Genetics of Antimicrobial Resistance. Topics to be Covered Antimicrobial Resistance Consequences of Antimicrobial Resistant Bacteria Change in the approach to the administration of empiric antimicrobial therapy Increased number of hospitalizations Increased length

More information

MID 23. Antimicrobial Resistance. Consequences of Antimicrobial Resistant Bacteria. Molecular Genetics of Antimicrobial Resistance

MID 23. Antimicrobial Resistance. Consequences of Antimicrobial Resistant Bacteria. Molecular Genetics of Antimicrobial Resistance Antimicrobial Resistance Molecular Genetics of Antimicrobial Resistance Micro evolutionary change - point mutations Beta-lactamase mutation extends spectrum of the enzyme rpob gene (RNA polymerase) mutation

More information

Antimicrobial Resistance

Antimicrobial Resistance Antimicrobial Resistance Consequences of Antimicrobial Resistant Bacteria Change in the approach to the administration of empiric antimicrobial therapy Increased number of hospitalizations Increased length

More information

Antimicrobial Resistance Acquisition of Foreign DNA

Antimicrobial Resistance Acquisition of Foreign DNA Antimicrobial Resistance Acquisition of Foreign DNA Levy, Scientific American Horizontal gene transfer is common, even between Gram positive and negative bacteria Plasmid - transfer of single or multiple

More information

Virulence Factors of Bordetella bronchiseptica Associated with the

Virulence Factors of Bordetella bronchiseptica Associated with the INFECTION AND IMMUNITY, Jan. 1987, p. 217-222 0019-9567/87/010217-06$02.00/0 Copyright 1987, American Society for Microbiology Vol. 55, No. 1 Virulence Factors of Bordetella bronchiseptica Associated with

More information

Probing the Function of Bordetella bronchiseptica Adenylate Cyclase Toxin by Manipulating Host Immunity

Probing the Function of Bordetella bronchiseptica Adenylate Cyclase Toxin by Manipulating Host Immunity INFECTION AND IMMUNITY, Mar. 1999, p. 1493 1500 Vol. 67, No. 3 0019-9567/99/$04.00 0 Copyright 1999, American Society for Microbiology. All Rights Reserved. Probing the Function of Bordetella bronchiseptica

More information

Role of the Type III Secretion System in a Hypervirulent Lineage of Bordetella bronchiseptica

Role of the Type III Secretion System in a Hypervirulent Lineage of Bordetella bronchiseptica INFECTION AND IMMUNITY, Sept. 2009, p. 3969 3977 Vol. 77, No. 9 0019-9567/09/$08.00 0 doi:10.1128/iai.01362-08 Copyright 2009, American Society for Microbiology. All Rights Reserved. Role of the Type III

More information

1. Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and

1. Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and JB Accepted Manuscript Posted Online 30 July 2018 J. Bacteriol. doi:10.1128/jb.00175-18 This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights

More information

Bordetella bronchiseptica: A Candidate Mucosal Vaccine Vector

Bordetella bronchiseptica: A Candidate Mucosal Vaccine Vector University of Tennessee, Knoxville Trace: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2002 Bordetella bronchiseptica: A Candidate Mucosal Vaccine Vector Sreekumari

More information

Antimicrobial agents

Antimicrobial agents Bacteriology Antimicrobial agents Learning Outcomes: At the end of this lecture, the students should be able to: Identify mechanisms of action of antimicrobial Drugs Know and understand key concepts about

More information

expression of bvg-regulated genes and an avirulent phenotype (15, 16). In this paper we report the complete nucleotide sequence

expression of bvg-regulated genes and an avirulent phenotype (15, 16). In this paper we report the complete nucleotide sequence Proc. Natl. Acad. Sci. USA Vol. 86, pp. 6671-6675, September 1989 Genetics Sequences required for expression of Bordetella pertussis virulence factors share homology with prokaryotic signal transduction

More information

Overview. There are commonly found arrangements of bacteria based on their division. Spheres, Rods, Spirals

Overview. There are commonly found arrangements of bacteria based on their division. Spheres, Rods, Spirals Bacteria Overview Bacteria live almost everywhere. Most are microscopic ranging from 0.5 5 m in size, and unicellular. They have a variety of shapes when viewed under a microscope, most commonly: Spheres,

More information

Methicillin-Resistant Staphylococcus aureus

Methicillin-Resistant Staphylococcus aureus Methicillin-Resistant Staphylococcus aureus By Karla Givens Means of Transmission and Usual Reservoirs Staphylococcus aureus is part of normal flora and can be found on the skin and in the noses of one

More information

Antimicrobial Resistance

Antimicrobial Resistance Antimicrobial Resistance Consequences of Antimicrobial Resistant Bacteria Change in the approach to the administration of Change in the approach to the administration of empiric antimicrobial therapy Increased

More information

Burton's Microbiology for the Health Sciences. Chapter 9. Controlling Microbial Growth in Vivo Using Antimicrobial Agents

Burton's Microbiology for the Health Sciences. Chapter 9. Controlling Microbial Growth in Vivo Using Antimicrobial Agents Burton's Microbiology for the Health Sciences Chapter 9. Controlling Microbial Growth in Vivo Using Antimicrobial Agents Chapter 9 Outline Introduction Characteristics of an Ideal Antimicrobial Agent How

More information

Molecular Characterization of Two Bordetella bronchiseptica Strains Isolated from Children with Coughs

Molecular Characterization of Two Bordetella bronchiseptica Strains Isolated from Children with Coughs JOURNAL OF CLINICAL MICROBIOLOGY, June 1997, p. 1550 1555 Vol. 35, No. 6 0095-1137/97/$04.00 0 Copyright 1997, American Society for Microbiology Molecular Characterization of Two Bordetella bronchiseptica

More information

Growth Phase- and Nutrient Limitation-Associated Transcript Abundance Regulation in Bordetella pertussis

Growth Phase- and Nutrient Limitation-Associated Transcript Abundance Regulation in Bordetella pertussis INFECTION AND IMMUNITY, Oct. 2006, p. 5537 5548 Vol. 74, No. 10 0019-9567/06/$08.00 0 doi:10.1128/iai.00781-06 Copyright 2006, American Society for Microbiology. All Rights Reserved. Growth Phase- and

More information

Synergistic Binding of RNA Polymerase and BvgA Phosphate to the Pertussis Toxin Promoter of Bordetella pertussis

Synergistic Binding of RNA Polymerase and BvgA Phosphate to the Pertussis Toxin Promoter of Bordetella pertussis JOURNAL OF BACTERIOLOGY, Nov. 1995, p. 6486 6491 Vol. 177, No. 22 0021-9193/95/$04.00 0 Copyright 1995, American Society for Microbiology Synergistic Binding of RNA Polymerase and BvgA Phosphate to the

More information

Lecture 6: Fungi, antibiotics and bacterial infections. Outline Eukaryotes and Prokaryotes Viruses Bacteria Antibiotics Antibiotic resistance

Lecture 6: Fungi, antibiotics and bacterial infections. Outline Eukaryotes and Prokaryotes Viruses Bacteria Antibiotics Antibiotic resistance Lecture 6: Fungi, antibiotics and bacterial infections Outline Eukaryotes and Prokaryotes Viruses Bacteria Antibiotics Antibiotic resistance Lecture 1 2 3 Lecture Outline Section 4 Willow and aspirin Opium

More information

Index. Note: Page numbers of article titles are in boldface type.

Index. Note: Page numbers of article titles are in boldface type. Index Note: Page numbers of article titles are in boldface type. A Abdominal viscera, examination of, in investigation of emerging infectious diseases of food animals, 6 American Veterinary Medical Association,

More information

Activation of the vrg6 Promoter of Bordetella pertussis by RisA

Activation of the vrg6 Promoter of Bordetella pertussis by RisA JOURNAL OF BACTERIOLOGY, Mar. 2005, p. 1648 1658 Vol. 187, No. 5 0021-9193/05/$08.00 0 doi:10.1128/jb.187.5.1648 1658.2005 Activation of the vrg6 Promoter of Bordetella pertussis by RisA Tadhg Ó Cróinín,

More information

Antimicrobial use in poultry: Emerging public health problem

Antimicrobial use in poultry: Emerging public health problem Antimicrobial use in poultry: Emerging public health problem Eric S. Mitema, BVM, MS, PhD CPD- Diagnosis and Treatment of Poultry Diseases FVM, CAVS, 6 th. August, 2014 AMR cont Antibiotics - Natural or

More information

SUMMARY OF PRODUCT CHARACTERISTICS

SUMMARY OF PRODUCT CHARACTERISTICS SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Oxycare 20 %w/v LA Solution for Injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Active Substance: Oxytetracycline (Equivalent

More information

An#bio#cs and challenges in the wake of superbugs

An#bio#cs and challenges in the wake of superbugs An#bio#cs and challenges in the wake of superbugs www.biochemj.org/bj/330/0581/bj3300581.htm ciss.blog.olemiss.edu Dr. Vassie Ware Bioscience in the 21 st Century November 14, 2014 Who said this and what

More information

Received 22 April 2011/Accepted 30 June 2011

Received 22 April 2011/Accepted 30 June 2011 JOURNAL OF BACTERIOLOGY, Sept. 2011, p. 4798 4812 Vol. 193, No. 18 0021-9193/11/$12.00 doi:10.1128/jb.05136-11 Copyright 2011, American Society for Microbiology. All Rights Reserved. Transcriptional Profiling

More information

THE COST OF COMPANIONSHIP

THE COST OF COMPANIONSHIP THE COST OF COMPANIONSHIP Jared Gillingham and Robert Burlage Concordia University School of Pharmacy Mequon, WI Synopsis: Infectious diseases are always a concern, but when you are a person in an at-risk

More information

R-factor mediated trimethoprim resistance: result of two three-month clinical surveys

R-factor mediated trimethoprim resistance: result of two three-month clinical surveys Journal of Clinical Pathology, 1978, 31, 850-854 R-factor mediated trimethoprim resistance: result of two three-month clinical surveys S. G. B. AMYES1, A. M. EMMERSON2, AND J. T. SMITH3 From the 'Department

More information

Inhibiting Microbial Growth in vivo. CLS 212: Medical Microbiology Zeina Alkudmani

Inhibiting Microbial Growth in vivo. CLS 212: Medical Microbiology Zeina Alkudmani Inhibiting Microbial Growth in vivo CLS 212: Medical Microbiology Zeina Alkudmani Chemotherapy Definitions The use of any chemical (drug) to treat any disease or condition. Chemotherapeutic Agent Any drug

More information

What is antimicrobial resistance?

What is antimicrobial resistance? What is antimicrobial resistance? Gérard MOULIN gerard.moulin@anses.fr French agency for food, environmental and occupationnal safety National agency for veterinary Medicinal Products BP 90203-35302 FOUGERES

More information

Burn Infection & Laboratory Diagnosis

Burn Infection & Laboratory Diagnosis Burn Infection & Laboratory Diagnosis Introduction Burns are one the most common forms of trauma. 2 million fires each years 1.2 million people with burn injuries 100000 hospitalization 5000 patients die

More information

WHY IS THIS IMPORTANT?

WHY IS THIS IMPORTANT? CHAPTER 20 ANTIBIOTIC RESISTANCE WHY IS THIS IMPORTANT? The most important problem associated with infectious disease today is the rapid development of resistance to antibiotics It will force us to change

More information

Regulated. bronchiseptica and B. pertussis. Deletion of bvgas or modulation. In this phase vag genes are not induced and vrg loci

Regulated. bronchiseptica and B. pertussis. Deletion of bvgas or modulation. In this phase vag genes are not induced and vrg loci JOURNAL OF BACTERIOLOGY, June 1993, p. 3468-3479 0021-9193/93/113468-12$02.00/0 Copyright 1993, American Society for Microbiology Vol. 175, No. 11 Flagellin Gene Transcription in Bordetella bronchiseptica

More information

Evaluation of a computerized antimicrobial susceptibility system with bacteria isolated from animals

Evaluation of a computerized antimicrobial susceptibility system with bacteria isolated from animals J Vet Diagn Invest :164 168 (1998) Evaluation of a computerized antimicrobial susceptibility system with bacteria isolated from animals Susannah K. Hubert, Phouc Dinh Nguyen, Robert D. Walker Abstract.

More information

Boosting Bacterial Metabolism to Combat Antibiotic Resistance

Boosting Bacterial Metabolism to Combat Antibiotic Resistance Boosting Bacterial Metabolism to Combat Antibiotic Resistance The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation As Published

More information

THE PENNSYLVANIA STATE UNIVERSITY SCHREYER HONORS COLLEGE DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY

THE PENNSYLVANIA STATE UNIVERSITY SCHREYER HONORS COLLEGE DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY THE PENNSYLVANIA STATE UNIVERSITY SCHREYER HONORS COLLEGE DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY THE ROLE OF FIMBRIAE IN BORDETELLA COLONIZATION MARGARET CURRY DUNAGIN Spring 2010 A thesis submitted

More information

1 In 1958, scientists made a breakthrough in artificial reproductive cloning by successfully cloning a

1 In 1958, scientists made a breakthrough in artificial reproductive cloning by successfully cloning a 1 In 1958, scientists made a breakthrough in artificial reproductive cloning by successfully cloning a vertebrate species. The species cloned was the African clawed frog, Xenopus laevis. Fig. 1.1, on page

More information

مادة االدوية المرحلة الثالثة م. غدير حاتم محمد

مادة االدوية المرحلة الثالثة م. غدير حاتم محمد م. مادة االدوية المرحلة الثالثة م. غدير حاتم محمد 2017-2016 ANTIMICROBIAL DRUGS Antimicrobial drugs Lecture 1 Antimicrobial Drugs Chemotherapy: The use of drugs to treat a disease. Antimicrobial drugs:

More information

The color and patterning of pigmentation in cats, dogs, mice horses and other mammals results from the interaction of several different genes

The color and patterning of pigmentation in cats, dogs, mice horses and other mammals results from the interaction of several different genes The color and patterning of pigmentation in cats, dogs, mice horses and other mammals results from the interaction of several different genes 1 Gene Interactions: Specific alleles of one gene mask or modify

More information

ESBL Producers An Increasing Problem: An Overview Of An Underrated Threat

ESBL Producers An Increasing Problem: An Overview Of An Underrated Threat ESBL Producers An Increasing Problem: An Overview Of An Underrated Threat Hicham Ezzat Professor of Microbiology and Immunology Cairo University Introduction 1 Since the 1980s there have been dramatic

More information

Doxivex, 100 mg/ml concentrate for oral solution for chickens and pigs

Doxivex, 100 mg/ml concentrate for oral solution for chickens and pigs 1 NAME OF THE VETERINARY MEDICINAL PRODUCT Doxivex, 100 mg/ml concentrate for oral solution for chickens and pigs 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Active substance: Quantity of active moiety:

More information

Martin Chénier, Ph.D. Microbiology. Antibiotics in Animal Production: Resistance and Alternative Solutions

Martin Chénier, Ph.D. Microbiology. Antibiotics in Animal Production: Resistance and Alternative Solutions Faculty of Agricultural and Environmental Sciences Department of Food Science, Department of Animal Science Martin Chénier, Ph.D. Microbiology Antibiotics in Animal Production: Resistance and Alternative

More information

Mechanism of antibiotic resistance

Mechanism of antibiotic resistance Mechanism of antibiotic resistance Dr.Siriwoot Sookkhee Ph.D (Biopharmaceutics) Department of Microbiology Faculty of Medicine, Chiang Mai University Antibiotic resistance Cross-resistance : resistance

More information

Microarray and Functional Analysis of Growth Phase-Dependent Gene Regulation in Bordetella bronchiseptica

Microarray and Functional Analysis of Growth Phase-Dependent Gene Regulation in Bordetella bronchiseptica INFECTION AND IMMUNITY, Oct. 2009, p. 4221 4231 Vol. 77, No. 10 0019-9567/09/$08.00 0 doi:10.1128/iai.00136-09 Copyright 2009, American Society for Microbiology. All Rights Reserved. Microarray and Functional

More information

Randall Singer, DVM, MPVM, PhD

Randall Singer, DVM, MPVM, PhD ANTIBIOTIC RESISTANCE Randall Singer, DVM, MPVM, PhD Associate Professor of Epidemiology Department of Veterinary and Biomedical Sciences University of Minnesota Overview How does resistance develop? What

More information

6.0 ANTIBACTERIAL ACTIVITY OF CAROTENOID FROM HALOMONAS SPECIES AGAINST CHOSEN HUMAN BACTERIAL PATHOGENS

6.0 ANTIBACTERIAL ACTIVITY OF CAROTENOID FROM HALOMONAS SPECIES AGAINST CHOSEN HUMAN BACTERIAL PATHOGENS 6.0 ANTIBACTERIAL ACTIVITY OF CAROTENOID FROM HALOMONAS SPECIES AGAINST CHOSEN HUMAN BACTERIAL PATHOGENS 6.1 INTRODUCTION Microorganisms that cause infectious disease are called pathogenic microbes. Although

More information

Presence of extended spectrum β-lactamase producing Escherichia coli in

Presence of extended spectrum β-lactamase producing Escherichia coli in 1 2 Presence of extended spectrum β-lactamase producing Escherichia coli in wild geese 3 4 5 A. Garmyn* 1, F. Haesebrouck 1, T. Hellebuyck 1, A. Smet 1, F. Pasmans 1, P. Butaye 2, A. Martel 1 6 7 8 9 10

More information

GeNei TM. Antibiotic Sensitivity. Teaching Kit Manual KT Revision No.: Bangalore Genei, 2007 Bangalore Genei, 2007

GeNei TM. Antibiotic Sensitivity. Teaching Kit Manual KT Revision No.: Bangalore Genei, 2007 Bangalore Genei, 2007 GeNei Bacterial Antibiotic Sensitivity Teaching Kit Manual Cat No. New Cat No. KT68 106333 Revision No.: 00180705 CONTENTS Page No. Objective 3 Principle 3 Kit Description 4 Materials Provided 5 Procedure

More information

Origins of Resistance and Resistance Transfer: Food-Producing Animals.

Origins of Resistance and Resistance Transfer: Food-Producing Animals. Origins of Resistance and Resistance Transfer: Food-Producing Animals. Chris Teale, AHVLA. Origins of Resistance. Mutation Brachyspira hyodysenteriae and macrolide and pleuromutilin resistance. Campylobacter

More information

Phenotypic Variation and Modulation in Bordetella bronchiseptica

Phenotypic Variation and Modulation in Bordetella bronchiseptica INFECTION AND IMMUNITY, June 1984, p. 681-687 0019-9567184/060681-07$02.00/0 Copyright C 1984, American Society for Microbiology Vol. 44, No. 3 Phenotypic Variation and Modulation in Bordetella bronchiseptica

More information

Bordetella bronchiseptica

Bordetella bronchiseptica JOURNAL OF CLINICAL MICROBIOLOGY, JUlY 1993, p. 1838-1844 0095-1137/93/071838-07$02.00/0 Copyright X) 1993, American Society for Microbiology Vol. 31, No. 7 Fimbriae and Determination of Host Species Specificity

More information

An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage

An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage Journal of Antimicrobial Chemotherapy (1991) 27, Suppl. C, 1-7 An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage J. J. Muscato",

More information

1/27/10 More complications to Mendel

1/27/10 More complications to Mendel 1/27/10 More complications to Mendel Required Reading: The Interpretation of Genes Natural History 10/02 pg. 52-58 http://fire.biol.wwu.edu/trent/trent/interpretationofgenes.pdf NOTE: In this and subsequent

More information

Staphylococcus aureus

Staphylococcus aureus Staphylococcus aureus Significant human pathogen. SSTI Biomaterial related infections Osteomyelitis Endocarditis Toxin mediated diseases TSST Staphylococcal enterotoxins Quintessential Pathogen? Nizet

More information

Antibacterial Agents & Conditions. Stijn van der Veen

Antibacterial Agents & Conditions. Stijn van der Veen Antibacterial Agents & Conditions Stijn van der Veen Antibacterial agents & conditions Antibacterial agents Disinfectants: Non-selective antimicrobial substances that kill a wide range of bacteria. Only

More information

Significant human pathogen. SSTI Biomaterial related infections Osteomyelitis Endocarditis Toxin mediated diseases TSST Staphylococcal enterotoxins

Significant human pathogen. SSTI Biomaterial related infections Osteomyelitis Endocarditis Toxin mediated diseases TSST Staphylococcal enterotoxins Staphylococcus aureus Significant human pathogen. SSTI Biomaterial related infections Osteomyelitis Endocarditis Toxin mediated diseases TSST Staphylococcal enterotoxins Quintessential Pathogen? Nizet

More information

Antibiotic Resistance in Bacteria

Antibiotic Resistance in Bacteria Antibiotic Resistance in Bacteria Electron Micrograph of E. Coli Diseases Caused by Bacteria 1928 1 2 Fleming 3 discovers penicillin the first antibiotic. Some Clinically Important Antibiotics Antibiotic

More information

Recommended for Implementation at Step 7 of the VICH Process on 15 December 2004 by the VICH Steering Committee

Recommended for Implementation at Step 7 of the VICH Process on 15 December 2004 by the VICH Steering Committee VICH GL27 (ANTIMICROBIAL RESISTANCE: PRE-APPROVAL) December 2003 For implementation at Step 7 - Final GUIDANCE ON PRE-APPROVAL INFORMATION FOR REGISTRATION OF NEW VETERINARY MEDICINAL PRODUCTS FOR FOOD

More information

[Version 8.1,01/2017] ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS

[Version 8.1,01/2017] ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS [Version 8.1,01/2017] ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Pneumospectin 50 mg/ml +100 mg/ml solution for injection for cattle (calves), sheep, goat, pig,

More information

Was the Spotted Horse an Imaginary Creature? g.org/sciencenow/2011/11/was-the-spotted-horse-an-imagina.html

Was the Spotted Horse an Imaginary Creature?   g.org/sciencenow/2011/11/was-the-spotted-horse-an-imagina.html Was the Spotted Horse an Imaginary Creature? http://news.sciencema g.org/sciencenow/2011/11/was-the-spotted-horse-an-imagina.html 1 Genotypes of predomestic horses match phenotypes painted in Paleolithic

More information

Electron Microscopic Observations on Ciliated Epithelium of Tracheal Organ Cultures Infected with Bordetella bronchiseptica

Electron Microscopic Observations on Ciliated Epithelium of Tracheal Organ Cultures Infected with Bordetella bronchiseptica Microbiol. Immunol. Vol. 33 (2), 111-121, 1989 Electron Microscopic Observations on Ciliated Epithelium of Tracheal Organ Cultures Infected with Bordetella bronchiseptica Kachiko SEKIYA,*,1 Yutaka FUTAESAKU,2

More information

The Disinfecting Effect of Electrolyzed Water Produced by GEN-X-3. Laboratory of Diagnostic Medicine, College of Medicine, Soonchunhyang University

The Disinfecting Effect of Electrolyzed Water Produced by GEN-X-3. Laboratory of Diagnostic Medicine, College of Medicine, Soonchunhyang University The Disinfecting Effect of Electrolyzed Water Produced by GEN-X-3 Laboratory of Diagnostic Medicine, College of Medicine, Soonchunhyang University Tae-yoon Choi ABSTRACT BACKGROUND: The use of disinfectants

More information

SUMMARY OF PRODUCT CHARACTERISTICS

SUMMARY OF PRODUCT CHARACTERISTICS SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Marbocare 20 mg/ml solution for injection for cattle and pigs (UK, IE, FR) Odimar 20 mg/ml solution for injection for cattle

More information

SELECT NEWS. Florfenicol Monograph: Injectable & Oral Therapy for Swine

SELECT NEWS. Florfenicol Monograph: Injectable & Oral Therapy for Swine SELECT NEWS Florfenicol Monograph: Injectable & Oral Therapy for Swine Did you know that? Florfenicol is one of the most powerful antibiotics currently available in veterinary medicine with one of the

More information

Influence of ph on Adaptive Resistance of Pseudomonas aeruginosa to Aminoglycosides and Their Postantibiotic Effects

Influence of ph on Adaptive Resistance of Pseudomonas aeruginosa to Aminoglycosides and Their Postantibiotic Effects ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 1996, p. 35 39 Vol. 40, No. 1 0066-4804/96/$04.00 0 Copyright 1996, American Society for Microbiology Influence of ph on Adaptive Resistance of Pseudomonas aeruginosa

More information

Antimicrobial Resistance and Prescribing

Antimicrobial Resistance and Prescribing Antimicrobial Resistance and Prescribing John Ferguson, Microbiology & Infectious Diseases, John Hunter Hospital, University of Newcastle, NSW, Australia M Med Part 1 updates UPNG 2017 Tw @mdjkf http://idmic.net

More information

Antibiotics: Conflict and Communication in Microbial Communities

Antibiotics: Conflict and Communication in Microbial Communities Antibiotics: Conflict and Communication in Microbial Communities Antibiotics mediate species interactions in natural habitats, affecting the dynamics of microbial coevolution Daniel C. Schlatter and Linda

More information

10/15/08. Activity of an Antibiotic. Affinity for target. Permeability properties (ability to get to the target)

10/15/08. Activity of an Antibiotic. Affinity for target. Permeability properties (ability to get to the target) Beta-lactam antibiotics Penicillins Target - Cell wall - interfere with cross linking Actively growing cells Bind to Penicillin Binding Proteins Enzymes involved in cell wall synthesis Activity of an Antibiotic

More information

The Search For Antibiotics BY: ASLEY, ELIANA, ISABELLA AND LUNISCHA BSC1005 LAB 4/18/2018

The Search For Antibiotics BY: ASLEY, ELIANA, ISABELLA AND LUNISCHA BSC1005 LAB 4/18/2018 The Search For Antibiotics BY: ASLEY, ELIANA, ISABELLA AND LUNISCHA BSC1005 LAB 4/18/2018 The Need for New Antibiotics Antibiotic crisis An antibiotic is a chemical that kills bacteria. Since the 1980s,

More information

Introduction to Chemotherapeutic Agents. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The university of Jordan November 2018

Introduction to Chemotherapeutic Agents. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The university of Jordan November 2018 Introduction to Chemotherapeutic Agents Munir Gharaibeh MD, PhD, MHPE School of Medicine, The university of Jordan November 2018 Antimicrobial Agents Substances that kill bacteria without harming the host.

More information

THE BOVINE MILK MICROBIOME. Mark McGuire

THE BOVINE MILK MICROBIOME. Mark McGuire THE BOVINE MILK MICROBIOME Mark McGuire FLOW OF MILK FROM A FARM TO PROCESSOR HOW TO ASSESS PRESENCE OF BACTERIA? Culture-dependent methods Culture-independent methods Rely on molecular techniques and

More information

SUMMARY OF PRODUCT CHARACTERISTICS

SUMMARY OF PRODUCT CHARACTERISTICS SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Enrocare 50 mg/ml Solution for Injection for Cattle, Pigs, Dogs and Cats (UK, IE, FR) Floxadil 50 mg/ml Solution for Injection

More information

Title: N-Acetylcysteine (NAC) Mediated Modulation of Bacterial Antibiotic

Title: N-Acetylcysteine (NAC) Mediated Modulation of Bacterial Antibiotic AAC Accepts, published online ahead of print on June 00 Antimicrob. Agents Chemother. doi:0./aac.0070-0 Copyright 00, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights

More information

ANTIBIOTIC RESISTANCE. Syed Ziaur Rahman, MD, PhD D/O Pharmacology, JNMC, AMU, Aligarh

ANTIBIOTIC RESISTANCE. Syed Ziaur Rahman, MD, PhD D/O Pharmacology, JNMC, AMU, Aligarh ANTIBIOTIC RESISTANCE Syed Ziaur Rahman, MD, PhD D/O Pharmacology, JNMC, AMU, Aligarh WHY IS THIS IMPORTANT? The most important problem associated with infectious disease today is the rapid development

More information

Pharm 262: Antibiotics. 1 Pharmaceutical Microbiology II DR. C. AGYARE

Pharm 262: Antibiotics. 1 Pharmaceutical Microbiology II DR. C. AGYARE Pharm 262: 1 Pharmaceutical Microbiology II Antibiotics DR. C. AGYARE Reference Books 2 HUGO, W.B., RUSSELL, A.D. Pharmaceutical Microbiology. 6 th Ed. Malden, MA: Blackwell Science, 1998. WALSH, G. Biopharmaceuticals:

More information

Eric T. Harvill, Dept. of Veterinary and Biomedical Sciences, Penn State. Vivek Kapur, Dept. of Veterinary and Biomedical Sciences, Penn State

Eric T. Harvill, Dept. of Veterinary and Biomedical Sciences, Penn State. Vivek Kapur, Dept. of Veterinary and Biomedical Sciences, Penn State Genomic Analysis of the Classical Bordetella Eric T. Harvill, Dept. of Veterinary and Biomedical Sciences, Penn State Vivek Kapur, Dept. of Veterinary and Biomedical Sciences, Penn State Ying Zhang, Dept.

More information

Bordetella evolution: lipid A and Toll-like receptor 4

Bordetella evolution: lipid A and Toll-like receptor 4 IEIIS Meeting minireview Bordetella evolution: lipid A and Toll-like receptor 4 Iain MacArthur 1, Paul B. Mann 2 *, Eric T. Harvill 2, Andrew Preston 1 1 Department of Molecular and Cellular Biology, University

More information

Fluoroquinolones resistant Gram-positive cocci isolated from University of Calabar Teaching Hospital, Nigeria

Fluoroquinolones resistant Gram-positive cocci isolated from University of Calabar Teaching Hospital, Nigeria GSC Biological and Pharmaceutical Sciences, 2017, 01(01), 001 005 Available online at GSC Online Press Directory GSC Biological and Pharmaceutical Sciences e-issn: 2581-3250, CODEN (USA): GBPSC2 Journal

More information

Running title: Contribution of Bordetella Bps to Biofilm Formation and Respiratory Disease in

Running title: Contribution of Bordetella Bps to Biofilm Formation and Respiratory Disease in IAI Accepted Manuscript Posted Online 30 May 2017 Infect. Immun. doi:10.1128/iai.00261-17 Copyright 2017 American Society for Microbiology. All Rights Reserved. 1 2 The Bordetella Bps Polysaccharide is

More information

Bovine Mastitis Products for Microbiological Analysis

Bovine Mastitis Products for Microbiological Analysis Bovine Mastitis Products for Microbiological Analysis 121917ss Hardy Diagnostics has everything for your laboratory! SAVE MONEY Now you have a choice for obtaining your supplies for mastitis testing. Hardy

More information

Selective toxicity. Antimicrobial Drugs. Alexander Fleming 10/17/2016

Selective toxicity. Antimicrobial Drugs. Alexander Fleming 10/17/2016 Selective toxicity Antimicrobial Drugs Chapter 20 BIO 220 Drugs must work inside the host and harm the infective pathogens, but not the host Antibiotics are compounds produced by fungi or bacteria that

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION doi:10.1038/nature12234 Supplementary Figure 1. Embryonic naked mole-rat fibroblasts do not undergo ECI. Embryonic naked mole-rat fibroblasts ( EF) were isolated from eight mid-gestation embryos. All the

More information

β-lactams resistance among Enterobacteriaceae in Morocco 1 st ICREID Addis Ababa March 2018

β-lactams resistance among Enterobacteriaceae in Morocco 1 st ICREID Addis Ababa March 2018 β-lactams resistance among Enterobacteriaceae in Morocco 1 st ICREID Addis Ababa 12-14 March 2018 Antibiotic resistance center Institut Pasteur du Maroc Enterobacteriaceae (E. coli, Salmonella, ) S. aureus

More information

(Received 24 February 1988)

(Received 24 February 1988) Journal of General Microbiology (1 988), 134, 2297-2306. Printed in Great Britain 2297 Nucleotide Sequence and Characterization of a Repetitive DNA Element from the Genome of Bordetella pertussis with

More information

New Washable SPILLSEAL Keyboards. How they can reduce MRSA in your hospital

New Washable SPILLSEAL Keyboards. How they can reduce MRSA in your hospital New Washable SPILLSEAL Keyboards How they can reduce MRSA in your hospital The Evaluation of Disinfection Procedures for SPILLSEAL Keyboards Contaminated with Staphylococcus Aureus Dr. Tony Moore, Head

More information

Chapter concepts: What are antibiotics, the different types, and how do they work? Antibiotics

Chapter concepts: What are antibiotics, the different types, and how do they work? Antibiotics Chapter concepts: Antibiotics What are antibiotics, the different types, and how do they work? How do we decided on the most appropriate antibiotic treatment? What are some of the ways that bacteria are

More information

POST SCREENING METHODS FOR THE DETECTION OF BETA-LACTAM RESIDUES IN PIGS.

POST SCREENING METHODS FOR THE DETECTION OF BETA-LACTAM RESIDUES IN PIGS. POST SCREENING METHODS FOR THE DETECTION OF BETA-LACTAM RESIDUES IN PIGS. Lorraine Lynas, Deborah Currie and John D.G. McEvoy. Department of Agriculture and Rural Development for Northern Ireland, Veterinary

More information