Staphylococcus 8/30/2011. The Genus Staphylococcus. Cell wall. S. aureus. + - Bunch of grapes + berry. Gram-positive aerobic cocci

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1 The Genus Staphylococcus Gram-positive aerobic cocci Staphylococcus Staphylococcus: Micrococcus Peptidococcus Pediococcus Catalase (2H2O2 2H2O + O2) + - Bunch of grapes + berry You will learn soon S. aureus Cell wall aureus means golden ; because of yellowish colony color Habitat - Skin of most mammals and some avian sp. - 30% of humans are nasal carriers - Also, present in the oral cavity Cultural characteristics - Grow best aerobically at 37ºC - Sheep blood agar is usually used for human isolates Polyribitol (C5) type Teichoic acids 30% ~ 50% the cell wall Polyglycerol (C3) type S. aureus S. epidermidis Peptidoglycan 50% ~ 60% the cell wall Teichoic acids O-acetylation of muramic acid High degree of cross-linking Complete resistance to lysozyme 1

2 MSCRAMMs Coagulase Microbial Surface Component Recognizing Adhesive Matrix Molecules - eg. Fibronectin-binding protein Collagen-binding protein - Interacting with host cells Coagulase and prothrombin form staphylothrombin fibrinogen (soluble) fibrin (insoluble) - + S. aureus colonizes the skin of mammals S. aureus infections often begin at some breach in the epithelial barrier MSCRAMMs enhance the bacterial attachment to host cells collagen fibronectin Host cells CoP staphylococci: S. aureus, S. intermedius, S. lutrae, S. pseudintermedius, S. delphini, and S. schleiferi ssp. coagulans (cf. S. schleiferi ssp. schleiferi is CN), S. hyicus (50%) - The most important indicator of clinical significance, but coagulase-negative staphylococci are still a major cause of wound infections and mastitis no longer a gold standard of pathogenicity of staphylococci Evasion of Phogocytosis Staphylococci possess virulence factors to avoid phagocytosis Evasion of Phogocytosis: Protein A Protein A: binds the Fc portion of the IgG antibodies Capsule - Polysaccharides on bacterial surface - Important virulence factors in many isolates :nonencapulated strains are less virulent in bovine mastitis - Capsule production is quickly lost in vitro O'Riordan and Lee, 2004 Antibody binding sites Fc portion Bacterium Protein A - Major component of the cell wall - Also found in S. intermedius - Binds to the Fc fragment of immunoglobulins - Biological effects: anticomplementary and antiphagocytic Protein A S. aureus Evade the immune response! 2

3 Toxins Double-Zone Hemolysis Toxins to kill or limit the ability of immune cells Leukocidin - kills neutrophils and macrophages by forming pores in the membrane but no other cell types Pus is killed neutrophils Hemolysins Double zone hemolysis by S. aureus Outer zone: incomplete hemolysis (alpha-hemolysis) Hemolysin Hemolysis Description α Complete (β) Forming transmembrane channels -Damaging many cell types - Nectrosis β Incomplete (α) Phospholipase C γ Complete (β) Hemolytic, found in 99% of S. aureus δ Complete (β) Strong detergent-like Inner zone: complete hemolysis (beta-hemolysis) S. intermedius and S. pseudintermdedius also produce double-zone hemolysis Superantigens Toxins that binds to MHC-TCR complexes with or without specific antigen bound, and even in the absence of presented antigens Stimulate large populations (up to20%) of T cells to produce cytokines Outpouring of cytokines at higher levels than normal Toxic shock syndrome: nausea, fever, myalgias, and death in humans its importance is not known in animals Antigen-presenting cell Toxins Superantigens Toxic shock syndrome toxin-1 (TSST-1) Enterotoxins A, B, C1, C2, C3, D, and E - causing gastroentestinal intoxication (food poisoning) - a lot less lethal than TSST-1 - rapid onset (a few hours of eating) and vomiting by stimulating nerves in the stomach - projectile vomiting and explosive diarrhea in humans Toxins contributing to the spread of bacteria Exfoliative toxins A, B, and C: - responsible for exfoliation of skin layers - causing scalded skin syndrome in newborn humans Staphylokinase (fibrinolysin): breaks down the fibrin barrier 3

4 Human Staphylococcal Infections S. aureus is the major species One of the most important pathogens involved in nosocomial infections Scalded skin syndrome - Exfoliative toxin exfoliative dermatitis: resulting in painful erythema and desquamation (skin peeling) - Children up to about 4 years of age Bacteremia: Dissemination of S. aureus into the bloodstream Endocarditis (infection of the heart valves): high mortality rates (40~80%) Metastatic abscessation: skin, subcutaneous tissues and lungs. sometimes in the brain, kidneys and spinal cord Food poisoning - Ingestion of contaminated food - Enterotoxins rapid (2~4 hrs) and severe cramping, vomiting, diarrhea Conjunctivitis, boils, otitis, sinusitis, cystitis, osteomyelitis Cattle - S. aureus: most common cause of mastitis Mastitis is initiated when organisms colonize damaged areas of the teat binding to epithelial cells progress through the teat duct, teat and milk ducts Subclinical mastitis: low milk production Clinical mastitis - Flakes or clots in the milk - Abnormal and hot udder, fever, loss of appetite, and death - Isolates from severe peracute mastitis shown to express TSST-1 (Toxic Shock Syndrome Toxin-1) and SEC (Staph Enterotoxin C) Dogs Skin infection, otitis externa, urogenital infection - Cause pyoderma ( pus in the skin ) in dogs The S. intermedius group - the S. intermedius group includes S. intermedius S. pseudintermedius (not pseudointermedius ) Pyoderma in dogs and S. delphini - S. pseudintermedius is the major pathogen in dogs based on genetic tests. Virtually all S. intermidius isolates from dogs are actually S. pseudintermedius Found routinely on the skin of normal dogs (opportunistic pathogen) Pigs Exudative epidermitis (greasy pig disease) - S. hyicus - Exfoliation of the skin, erythema, and exudation of serum Loss of the skin predisposes to other infections - Young (5 60 days) pigs : vaginal colonization infection of neonates - High mortality rate (5 ~ 90%) Mammary infection ingestion by newborn pubs pubs may develop septicemia and die acutely 4

5 Treatment and Immunity Cats - Abscesses, urinary tract infections - The S. intermedius group Horses - Pyoderma (skin infection producing pus) - The S. intermedius group Poultry - Arthritis and septicemia - Bumblefoot: chronic pyogranulomatous infection of soft subcutaneous tissues causing lameness and foot swelling - S. aureus Bumblefoot Treatment - Abscessation: difficult to treat - Penicillin used to be the drug of choice, but now almost all isolates are resistant to it - Ampicillin, novobiocin, chloramphenicol (non-foodproducing animals), florfenicol, cephalosporins - Multidrug resistance in both human and veterinary staphylococci - MRSA (methicillin-resistant S. aureus) - Use vancomycin resistance developed Immunity - No satisfactory immunizing agents are currently on the market - Bacterin products are available for mastitis in dairy cattle may decrease the severity of disease but does not prevent infection Staphylococcus Summary MRSA skin MSCRAMMs: Binding to host cells Capsule and Protein A: Evasion of host immune system How can MRSA become resistant to methicillin? - The meca gene produces an altered penicillin binding protein (PBP2a or PBP2 ), a bifunctional transglycosylase/transpeptidase reduce the affinity of β-lactam antibiotics conferring resistance Transglycosylase Production of various toxins Transpeptidase Peptide - Skin infection, bacteremia - Mastitis Endocarditis, food poisoning - S. aureus - S. aureus - Exudative epidermitis - S. hyicus -Skin infection -S. pseudintermedius 5

6 MRSA Many evidences of zoonotic transmission humans animals (pet and livestock animals) MRSA 6