Dier & Kruid Prof. Dr. J. Fink-Gremmels DVM, PhD, Dip ECVPT
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1 Dier & Kruid Prof. Dr. J. Fink-Gremmels DVM, PhD, Dip ECVPT
2 Antibiotics secondary metabolites produced under conditions of stress Fungi imperfecti (Penicillium Fusarium) Streptomyces Actinomyces spp Myxobacteria: Soragium cellulosum
3 AMR part of the natural homeostasis Co-evolution of bacteria and antimicrobial resistance Fungi: natural antibiotics Bacteria: adaptive AMR
4 2012
5 Bacterial communication systems biofilms and more!
6 Outside a laboratory in the real world Biofilms are prefect niches to survive!.. and to exchange resistance genes
7 Biofilms: in modern animal facilities Sub-MIC concentrations of antibiotics/disinfectants stimulate biofilm formation (also in slaughter houses) Oral medication via Drinking water: Biofilms and horizontal transmission of resistant organisms within a herd
8 Biofilms in daily veterinary practice Biofilms In the animal units Drinking water medication as a risk factor? Chronic respiratory tract infections APP Pasteurella Mycoplasma
9 Almost all pathogens are able to form biofilms
10 S. aureaus (MSSA, MRSA) S. pseudo-epidermidis (MSSP, MRSP) (dematitis, otitis (dog, cats) E.coli (UTI) Pseudomonas spp Campylobacter spp. Mycoplasma spp. Haemophilus parasuis Actinobacillus pleuropneumonia e.a. Biofilm characteristics - significant shift in antimicrobial sensitivity (MIC versus BMIC)
11 Staphylococcus aureus Mastitis N Penicillin MIC BMIC MBEC 1d MBEC 2d MBEC 4d Melchior & Fink-Gremmels, 2008)
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15 Wu et al., 2015
16 gwe gee allicin
17 TCM/CHM & Biofilm: Thesis X. Wu, 2015
18 Clinical relevance Biofilms determine of antimicrobial susceptibility Therapy-resistance; transfer of resistance genes Biofilms are not detected by common culture methods misleading therapeutic outcome monitoring? Biofilms are not detected by the immune system development of chronic recurrent infections
19 Clinically important biofilm sites in veterinary target species Wu et al., 2015
20 Biofilms: take-home messages I A biofilm is the most convenient form of life for bacteria Biofilms modulate the susceptibility of bacteria to (all) antimicrobial agents due to the Barrier effect of the extracellular matrix Gene shift in the dormant stage and virtually no proliferation Rapid transfer of genes within a biofilm community
21 Recent developments: Biofilm genes: an opportunity to modulate virulence? Plant-derived QS inhibitors may prevent biofilm formation and restore/improve the efficiency of antibiotics
22 Plant metabolites the natural QS inhibitors X. Wu et al, 2014 Yarwood J M et al. J. Bacteriol. 2004;186:
23 Quorum sensing inhibitors: An emerging therapeutic target Planktonic cells Inhibition of major Autoinducers Gram + agr (RNAIII)- auto-inducing peptides (AIP) Proto type: TP-1 Hamamelitannin = inhibitor of MRSA & MRSP QS-inhibitors Gram Acyl-homoserine lactones (AHL) LuxR Proto type: SAM-analoga, Cranberry! ADHESION & Expression of virulence factors inhibited Interspecies communication: LuxS/AI-2 signaling Inter-kingdom signalling: AI-3/epinephrine/norepinephrine i.e. Salmonella, E. coli, Shigella a.o.
24 Understanding te interactions between host & microorganism microorganisms & microorganisms QS determines the life-style: planctonic or biofilm The expression of virulance factors Pathogenicity Bacterial quorum sensing senses host signals (stress)
25 Limitations of in vitro testing: Acquisition of resistance genes in a complex environment Hypothesis: Protozoa may promote horizontal gene transfer E. coli J 53 acceptor qnr positive E.coli and Klebsiella as donors Result: The ciliated protozoan promotes the transfer of plasmid-mediated quinolone resistance In bacteria (as well as ESBLCTX-M-27: Oguri et.al., 2011, JAC 2011:66: ) Dietary factors modifying bacterial Gene expression: Plant metabolites (inhibitory) Cd, Zinc = stimulating?, Emerging infectious diseases, Marc, 2015
26 Collateral effects? bacteriën, > species 50 km schimmeldraden, > 500 species Planten groei planten ziekten algen > 500 species aaltjes > 50 species anderen bacteria, > 500 species 10 x more than body cells Reservoir for resistant organisms/ resitance genes
27 ??????? Question: Do we want to establish a biofilm working group: plant/extracts in the prevention of biofilm & as therapeutic support for biofilm infections.
Pathogens commonly isolated from selected diseases
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