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STAPHYLOCOCCUS n Staphylococcus causes diseases ranging from minor skin infections to life-threatening infections such as pneumonia, endocarditis, meningitis, postoperative wound infections, septicemia, and toxic shock syndrome. n Staphylococci are infrequently isolated from the oral cavity. n Spherical Gram-positive cocci arranged in irregular grape-like clusters.

Gram-staining of Staphylococus aureus

STAPHYLOCOCCUS n Facultative anaerobes - tolerate oxygen because they produce catalase (catalase positive). n They are non-motile (no flagella, no pili). n They are present on the skin and mucous membranes.

Three species of staphylococci are human pathogens: n S. aureus, S. epidermidis, S. saprophyticus. n S. aureus - the most virulent and best-known member of the genus, coagulase-positive (golden colonies as a result of carotenoid pigment). n The others are known as coagulase-negative cocci.

STAPHYLOCOCCUS n Capsule - (polysaccharide) inhibits chemotaxis and phagocytosis, facilitates attachment to catheters and other synthetic materials (a "slime layer" - the extracellular polymer; e.g. Staph. epidermidis). n Peptidoglycan - endotoxin-like activity, attracts polymorphonuclear leukocytes (abscess formation) and activates complement. n Lysozyme - in mucosal secretions (tears, saliva) - a natural barrier to staphylococcal infections. (an enzyme that destroys bacterial cell walls by hydrolyzing the polysaccharide component of the cell wall)

STAPHYLOCOCCUS n Protein A - the major protein in the cell wall of S. aureus. It binds to the Fc portion of IgG and prevents the antibody-mediated immune response. n Teichoic acids - (phosphate-containing polymers) bind to fibronectin and mediate attachment of staphylococci to mucosal surfaces. n Clumping factor (bound coagulase) binds fibrinogen.

Structure of staphylococcal cell wall

Staphylococcal Toxins - Exotoxins : n Cytolytic toxins (membrane damaging toxins, hemolysins): a (vasodilation, redness of skin), b (shingomyelinase C), d (membrane detergent), g, leukocidin. n Exfoliative (epidermolytic) toxin (desquamation) (”staphylococcal scalded skin syndrome”). n Toxic shock syndrome toxin-1 (TSST-1) (superantigen). n Enterotoxin - resistant to hydrolysis by GIT enzymes, n heat-stable (100°C for 30 min), stimulates vomiting center.

Staphylococcal Enzymes : n Coagulase - (bound and free) - converts fibrinogen to insoluble fibrin (clots plasma). n Catalase - converts H 2 O 2 into H 2 O and O 2 (streptococci are catalase negative). n Hyaluronidase - hydrolyzes hyaluronic acids (acidic mucopolysaccharides present in connective tissue). Facilitates the spread of S. aureus in tissues. n Fibrinolysin - staphylokinase, can dissolve fibrin clots.

Staphylococcal Enzymes: n Lipase - breaks lipids of cell membranes, invasion into cutaneous and subcutaneous tissues and the formation of superficial skin infections. n Nuclease (DNAse) - DNA hydrolysis. n Penicillinase (ß-lactamase) - resistance to penicillin.

Epidemiology n Staphylococci are widely present; coagulase-negative staphylococci on the skin surface and transient colonization of moist skin folds with S. aureus. n S. aureus and coagulase-negative staphylococci are found in naso- and oropharynx, gastrointestinal tract (GI), and urogenital tract. Approx. 15% (40%) of healthy adults are persistent nasopharyngeal carriers of S. aureus (hospitalized patients, medical personnel, individuals who regularly use needles). n Hospitalized patients are at particular risk; over 500,000 nosocomial (hospital-acquired) infections are reported per year.

Transmission n Respiratory droplets, fomites (contaminated clothing or bed linen). n Staphylococci are carried on the skin and in the nasopharynx. Shedding of bacteria is common and is responsible for many hospital infections. Cleanliness, hand washing and aseptic management of lesions reduce the spread of staphylococci.

Clinical Syndromes Staphylococcus aureus Diseases are caused by: n Production of toxin n Direct invasion and destruction of tissue

Diseases caused by toxins n Staphylococcal scalded skin syndrom (SSSS) (Ritter's disease; Bullous impetigo - a localized form of SSSS. n Toxic shock syndrome - TSST-1 toxin (1980/menstruating women; hyperabsorbing tampons). n Staphylococcal food poisoning (processed meat, ice cream).

Staphylococcal scalded skin syndrome (SSSS) Ritter’s disease Exfoliative dermatitis

Bullous impetigo, a localized form of staphylococcal scalded skin syndrome

Toxic shock syndrome A fatal infection with cutaneous and soft tissue involvement

Enterotoxins n Contamination of the food by a human carrier; 50% of carriers are asymptomatic, colonization mainly in the nasopharynx. n After ingestion of contaminated food the onset of disease is abrupt and rapid - performed toxin [severe vomiting, diarrhea, abdominal pain, nausea]. n The enterotoxins are heat stable - heating of the food will kill bacteria but not inactivate the heat- stable toxin.

Cutaneous Infections (typical lesion is an abscess) n Impetigo, folliculitis (a stye) n Furuncles (boils), carbuncules (carbunculosis) n Surgical wound infections, postpartum breast infections n Rarely oral infections (angular cheilitis together with the fungus Candida)

P Pustular impetigo

Systemic Infections n Bacteremia and endocarditis n Pneumonia and empyema n Osteomyelitis and arthritis

Staphylococcal diseases Endocarditis Staphylococcal scalded skin syndrome Pneumonia Staphylococcal food poisoning Toxic shock syndrome Cutaneous infections Septic arthritis

Staphylococcus epidermidis n Part of the normal human flora on the skin and mucous membranes. n Can cause infections of intravenous catheters and prosthetic implants e.g. heart valves. n Staph. epidermidis may adhere to medical devices through the production of biofilms.

Staph. epidermidis n Endocarditis (artificial valves) n Catheter and shunt infections n Prosthetic join infections Staph. saprophyticus - urinary tract infections - particularly in sexually active young women. It is a second cause of community-acquired urinary tract infections in this population (the first one is E. coli).

STAPHYLOCOCCUS - Treatment “SUPER BUG” In the U.S. >90% of Staph. aureus strains are resistant to penicillin. Development of semisynthetic penicillins resistant to lactamases (methicillin, naficillin, oxacillin). Emergence of methicillin resistant Staph. aureus (MRSA) %. Vancomycin - resistant Staph. aureus was isolated for the first time in Zyvox (generic name linezolid) - approved by the Food and Drug Administartion (FDA ) in 2000, especially for vancomycin resistant Enterococcus faecium (VREF).

Vancomycin resistance probably jumped from E. feacalis to S. aureus via a plasmid (black loop) carrying a transposon (red) that then infested the resident plasmid (blue)