Gram-Positive Bacterial Pathogens

Overview

Gram-positive bacteria are a major group of clinically significant microbes that stain purple in the Gram stain due to their thick peptidoglycan cell wall. They are classified based on their DNA content into two groups: low G+C and high G+C bacteria.

• Low G+C bacteria: Staphylococcus, Streptococcus, Enterococcus, Bacillus, Clostridium, Listeria, Mycoplasma

• High G+C bacteria: Corynebacterium, Propionibacterium, Nocardia, Actinomyces

Exotoxins

Exotoxins are potent, secreted proteins produced by many Gram-positive pathogens. They play a key role in disease pathogenesis.

• Exfoliative Toxins (Staph): Cause skin cell separation.

• Erythrogenic Toxins (Strep): Induce rash and fever.

• Botulinum Toxin: Neurotoxin causing flaccid paralysis.

• Toxic Shock Syndrome Toxin (Staph): Causes systemic shock.

• Enterococcus Cytolysin: Damages host cells.

• Listeriolysin O: Allows escape from phagosome.

Staphylococci

Structure and Physiology

Staphylococci are non-motile, facultative anaerobes and part of the normal microbiota of skin, respiratory, GI, and urogenital tracts. They are opportunistic pathogens.

• Common species: Staphylococcus aureus (pathogenic), Staphylococcus epidermidis (commensal)

Pathogenicity of S. aureus

Phagocytosis Evasion

• Protein A: Binds IgG, inhibits opsonization and complement activation.

• Bound coagulase: Converts fibrinogen to fibrin, forming clots that hide bacteria.

• Capsules: Inhibit leukocyte chemotaxis and phagocytosis; facilitate attachment.

Enzymes

• Cell-free coagulase: Triggers blood clotting.

• Hyaluronidase: Breaks down hyaluronic acid, aiding tissue spread.

• Staphylokinase: Dissolves fibrin clots, allowing escape.

• Lipases: Digest lipids, enabling growth on skin/oil glands.

• β-lactamase: Breaks down penicillin, conferring resistance to β-lactam drugs.

Toxins

• Cytolytic toxins (α, β, γ, δ, leucocidin): Disrupt cell membranes; leucocidin lyses leukocytes.

• Exfoliative toxins: Break desmosomes, causing skin sloughing.

• Toxic-shock syndrome toxin: Causes TSS.

• Enterotoxins: Cause food poisoning symptoms.

Virulence Factor Comparison Table

Epidemiology

• S. epidermidis: Ubiquitous on skin.

• S. aureus: Found in moist skin folds.

• Both species colonize upper respiratory, GI, and urogenital tracts.

• Transmission: Direct contact or fomites.

• Prevention: Handwashing and aseptic techniques.

Diseases

Noninvasive

• Food poisoning: Ingestion of enterotoxin-contaminated food.

Cutaneous

• Scalded skin syndrome: Exfoliative toxin-mediated skin sloughing.

• Impetigo: Pustular skin infection (80% staphylococcal).

• Folliculitis: Infection of hair follicles.

Systemic

• Toxic-shock syndrome (TSS): Systemic effects of TSS toxin.

• Bacteremia: Bloodstream infection, often healthcare-associated.

• Endocarditis: Infection of heart valves (50% mortality).

• Pneumonia/Empyema: Lung infection; empyema is pus accumulation.

• Osteomyelitis: Bone marrow and bone infection.

Diagnosis, Treatment, and Prevention

• Diagnosis: Gram-positive, grape-like clusters in samples; positive coagulase test.

• Treatment: Methicillin (semisynthetic penicillin); vancomycin for MRSA.

• Prevention: Hand antisepsis to prevent spread.

Streptococcus

Epidemiology

• Infects pharynx or skin when normal microbiota are disrupted.

• Transmission: Respiratory droplets.

Structure and Physiology

• Facultative anaerobes.

• Lancefield classification: Groups A (Streptococcus pyogenes), B (Streptococcus agalactiae), and others.

Group A (Streptococcus pyogenes) Pathogenicity

Phagocytosis Evasion

• M protein: Destabilizes complement, interferes with opsonization and lysis.

• Hyaluronic acid capsule: Hides bacteria from leukocytes.

Enzymes

• Streptokinases: Break down blood clots.

• C5a peptidase: Decreases inflammation, limits leukocyte recruitment.

• Hyaluronidase: Facilitates tissue spread.

• Deoxyribonucleases: Reduce pus firmness, facilitate spread.

Toxins

• Pyrogenic/erythrogenic toxins: Stimulate cytokine release, causing rash and shock.

• Streptolysins: Lyse RBCs, WBCs, platelets; damage host tissues.

Group A Diseases

• Pharyngitis ("strep throat"): Inflammation of pharynx, tonsils, fever, malaise.

• Scarlet fever: Rash, strawberry tongue (erythrogenic toxin).

• Rheumatic fever: Autoimmune response damaging heart valves/muscle.

• Pyoderma, erysipelas, cellulitis: Skin infections of varying depth and severity.

• Streptococcal Toxic Shock Syndrome (STSS): Multisystem infection, high mortality.

• Necrotizing fasciitis: "Flesh-eating strep"; rapid tissue destruction.

• Glomerulonephritis: Immune complex deposition in kidneys.

Diagnosis, Treatment, and Prevention

• Diagnosis: Gram-positive chains/pairs in skin infections; rapid strep test for respiratory.

• Treatment: Penicillin (or cephalosporin/erythromycin if allergic); surgical intervention for severe cases.

• Prevention: Antibodies against M protein protect against same strain.

Group B (Streptococcus agalactiae)

Epidemiology

• Colonizes GI and urogenital tracts.

• Infections in newborns (bacteremia, meningitis, pneumonia) and immunocompromised adults.

Diseases

• Neonatal bacteremia, meningitis, pneumonia; permanent neurological damage possible.

Diagnosis, Treatment, and Prevention

• Serology to identify group B.

• Penicillin or ampicillin (higher dose than for group A).

• Prophylactic penicillin during childbirth; immunization of women can protect children.

Viridans Group Streptococcus sp.

• Normal microbiota of mouth, pharynx, GI, urogenital tracts.

• Alpha-hemolytic, lack group-specific carbohydrates.

• Diseases: Dental caries (Streptococcus mutans), rare meningitis/endocarditis.

Streptococcus pneumoniae

Structure and Physiology

• Normal microbiota of upper respiratory tract; causes disease when entering lungs.

• Diplococci, capsule, alpha-hemolytic, lacks Lancefield antigens.

Pathogenicity

• Polysaccharide capsule: Prevents phagocytosis.

• Phosphorylcholine: Stimulates phagocytosis but allows intracellular survival.

• Protein adhesin: Binds to epithelial cells.

• IgA protease: Destroys IgA antibodies.

• Pneumolysin: Lyses epithelial cells.

Diseases

• Pneumococcal pneumonia: Most common disease.

• Sinusitis and otitis media: Often post-viral.

• Bacteremia and endocarditis: Entry via tissue damage.

• Pneumococcal meningitis: High mortality rate.