MICROBIO 3.3 - GRAM POSITIVE COCCI

• Gram-Positive cocci are bacteria with a spherical shape which retain the crystal violet stain in the Gram staining process.

Infections: Staphylococcus

• Gram-positive cocci infections are often attributed to Staphylococcus.
• Staphylococcus exhibits the following characteristics: it grows in clusters, is catalase-positive, non-motile, and does not form spores.
• Staphylococcus aureus is a virulent strain, and the cause of numerous infections and is coagulase-positive.
• Methicillin-resistant S. aureus (MRSA) is resistant to methicillin.
• S. Aureus has a distinctive golden color when grown on a petri dish with soy agar.

Staphylococcus aureus Virulence Factors

• Capsule; a structural component which inhibits phagocytosis.
• Biofilm allows the cells to firmly adhere to bacterial colonies reinforcing adhesion to the host and protects from immune cells as well as antibiotics
• Teichoic acid in its cell wall binds fibronectin.
• Lipoteichoic acid & peptidoglycan are endotoxin-like that trigger macrophages to release pro-inflammatory cytokines. Can help with adhesion by binding fibronectin.
• Protein A binds to the Fc portion of antibodies, preventing opsonization and complement activation.
• Coagulase enzyme converts fibrinogen to fibrin, promoting clot formation.
• Fibrinolysin (Staphylokinase) has the opposite effect, dissolving fibrin clots, potentially aiding the spread to other sites in the host.
• Hyaluronidase degrades hyaluronic acid in the host's extracellular matrix.
• Lipase inhibits host immune cells, inactivates bactericidal lipids, and promotes biofilm formation.
• Nuclease hydrolyzes DNA and aids in the evasion of Neutrophil Extracellular Traps (NETs).
• Cytotoxins such as alpha, beta, delta, gamma, and Panton-Valentine leukocidin lyse red and white blood cells.

Superantigens

• Superantigens cause excessive activation of the immune system.
• Exfoliative toxins (A & B) are proteases that destroy the granular layer of the epidermis.
• Enterotoxins stimulate T-cell and macrophage release of cytokines and trigger mast cell degranulation leading to peristalsis and vomiting.
• Toxic shock syndrome toxin-1 (TSST-1) stimulates T cell proliferation and the release of cytokines, causing blood vessel leakage.

Purulent Diseases

• Purulent diseases include conditions like impetigo (face/limbs with flat, red areas with pustules), folliculitis (hair follicle infection), furuncles/boils (raised, pus-filled), and carbuncles (deeper tissues; bacteremia).

Non-Skin Infections

• Acute Endocarditis is where bacteria & cellular debris accumulate & damage cardiac valves, block blood flow, and have clots break free.
• Pneumonia: infiltrates &/or abscesses that is caused by cell-damaging toxins & enzymes; some patients create empyema with accumulation of pus in the pleural cavity.
• Osteomyelitis: infects bones; early onset causes pain & fever and involves metaphyseal area of long bones in children and vertebral bodies in adults; Brodie's abscesses can be produced with localized infection within the bone.
• Septic Arthritis typically involves long joints.

Toxin Mediated Diseases

• Scalded skin syndrome (Ritter's disease) is from exfoliative toxins that affect newborns/young children and antibodies appear in 7-10 days, scarring is unusual, & mortality is low. Onset is abrupt & begins with perioral inflammatio;n superficial cutaneous blistering can happen with superficial cutaneous blistering & epithelial desquamation.
• Food poisoning is an ingestion of enterotoxins, which produce nausea, vomiting, and diarrhea.
• Toxic-shock syndrome is where TSST penetrates mucosal barriers & induces fever, rash, hypotension & shock; travels in blood, causing damage to multiple organ systems.

Treatment

• Gram-positive bacteria are vulnerable to antibiotics that target of cell wall.
• Penicillin is a beta-lactam antibiotic, although Methicillin is no-longer available due to side effects that is associated with kidney failure.
• Cephalosporins are beta-lactam antibiotics.
• Carbapenem is a beta-lactam that is used for multi-drug resistant (MDR) bacteria (similar in structure to penicillin).
• Vancomycin is a glycopeptide antibiotic, indicated for penicillin-allergic patients.
• Linezolid inhibits initiation of bacterial protein synthesis.
• Clindamycin slows or stops the growth of bacteria and is topical.

Coagulase-Negative Staphylococcus

• Prosthetic joint and valve infections are associated with Coagulase-Negative Staphylococcus.
• Staphylococcus epidermidis is common normal skin flora; that can cause boils, impetigo, cellulitis, scalded skin syndrome
• Staphylococcus saprophyticus causes urinary tract infections (UTI) in sexually active young women.
• Staphylococcus lugdunensis can cause native valve endocarditis.
• Staphylococcus haemolyticus can cause catheter-associated UTI.

Infections: Streptococcus pyogenes

• Streptococcus pyogenes are a gram-positive cocci infection.
• Characterized as: Pairs/Chains, Facultative anaerobes, Catalase negative.
• Hemolysis groups include Lancefield Serologic Groupings and beta-hemolytic streptococci is determined based on C-carbohydrate in the cell wall.

Streptococcus Pyogenes (Group A Strep) Virulence Factors:

• M protein blocks complement and phagocytosis.
• Hyaluronic acid capsule also inhibits phagocytosis.
• Lipoteichoic acid and F protein binds fibronectin.
• M & F proteins facilitate epithelial cell invasion.
• M-like surface proteins bind fibronectin and antibodies.
• Streptococcal pyrogenic exotoxins is a superantigen.
• Streptolysin S & O lyse blood cells.
• Streptokinases A & B are enzymes that break up blood clots to promote bacterial spread.
• DNases reduce pus viscosity that promotes bacterial spread.

Streptococcus pyogenes Virulence Factors Diseases

• Streptococcal pharyngitis ("strep throat") will have throat & tonsil inflammation with with swollen cervical lymph nodes along with fever & headache.
• Scarlet fever is a complication of strep pharyngitis with rash that appears on chest and limbs.
• Rheumatic fever is a strep throat/scarlet fever complication with inflammation of joints & blood vessels.

Streptococcus Skin Disease

• Impetigo has reddened areas with pustules that crust upon rupture.
• Cellulitis includes skin that is red, swollen, & warm to the touch that is usually both painful and can spread within deep tissues.
• Erysipelas includes raised red lesions, typically on the face/legs and fever and chills.
• Necrotizing fasciitis ("streptococcal gangrene") results in infections that spread to deeper tissues, which can cause multi-organ failure & death.

Complications due to Streptococcus

• Streptococcal Toxic Shock Syndrome (STSS) with pyogenic exotoxins results in chills, vomiting & diarrhea with bacteremia & necrotizing fasciitis. Staph TSS mortality is at Staph TSS mortality= <3%, but Strep TSS mortality is 30-70%. Treatment involves IV penicillin & clindamycin as well as intravenous fluids & surgery.
• Heart disease causes inflammation of cardiac tissues that can damage the cardiac valves and block blood flow.
• Acute glomerulonephritis can present inflammation for edema, hypertension, hematuria, & proteinuria.

S. pneumoniae Alpha Hemolytic Optochin sensitive

• S. Pneumoniae, also known as Pneumococcus.
• Its Virulence factors include:
• IgA protease- degrades IgA to allow bacteria to reach mucous membranes of respiratory & genital tract
• Pneumolysin- lyses phagocytic cells & respiratory epithelium
• Produces hydrogen peroxide to damage host tissues
• Phosyphorylcholine- facilitates entry into host cells to evade detection
• Can result in pneumonia, otitis media and sinusitis, or pneumococcal meningitis
• Preventative treatment involves Penicillin (Beta-lactam) or Ceftriaxone (cephalosporin antibiotic) or Pneumococcal vaccine.

Viridans Streptococcus Alpha Hemolytic Optochin resistant

• Viridans is from Latin "viridis" green.
• Diseases include deep tissue abscesses, bacteremia in cancer patients with neutropenia, subacute endocarditis, and tooth decay
• Viridans Strep are vulnerable to antibiotics but S. mitis is has antibiotic-resistance.

Beta-Hemolytic Bacitracin Resistant: S. agalactiae

• S. agalactiae is also known as "Group B strep".
• Commonly colonizes the colon & genitourinary tracts of women which can be passed to neonate during labor.
• Early-onset diseases occur within the first 7 days after birth and include bacteremia, pneumonia, & meningitis and is typically from labor/birth.
• Late-onset diseases occur between I week & 3 months of age & include bacteremia with meningitis
• Can also cause post-partum endometritis, and Group B streptococcus is associated with bacteremia leading to pneumonia & infections of the bones and joints.
• Treatment involves Penicillin or Cephalosporins.

Gamma Hemolytic: Enterococcus

• Resistant to most antibiotics and less virulent than other Gram+ cocci.
• Factors include: biofilm, adherence to host tissues, and forming a biofilm.
• Enterococcus can cause: urinary tract infections, bacteremia, endocarditis, and peritonitis