15.6 Bacterial Role in Disease

Pathogenesis: The Chain of Infection

Bacterial disease requires a sequence: encounter → entry → adherence → evasion → multiplication → damage → exit. Each step has a corresponding virulence factor, and the PA-CAT Bulletin of Information, rev. 20240815, expects you to connect specific factors to clinical syndromes. The PA-CAT sample item — a 13-year-old with sore throat followed by a rash with pink rings and clear centers and elevated ASO antibodies — points to Streptococcus pyogenes (Group A strep) causing rheumatic fever, an archetype of immune-mediated post-infectious disease.

Virulence Factors at a Glance

Capsules

A capsule is an extracellular polysaccharide (or polypeptide, in Bacillus anthracis) layer that resists phagocytosis by blocking complement deposition and opsonin recognition. Encapsulated organisms — S. pneumoniae, N. meningitidis, H. influenzae type b, Klebsiella, B. anthracis — cause invasive disease when capsule is present and are controlled by capsule-specific antibody (basis of conjugate vaccines).

Toxins: Endotoxin vs. Exotoxin

Endotoxin Pathophysiology

Lipid A of LPS binds LPS-binding protein (LBP) in plasma, which transfers it to CD14/MD2 on macrophages and monocytes, activating TLR4. The resulting cytokine storm — TNF-α, IL-1, IL-6 — produces fever, hypotension, capillary leak, myocardial depression, disseminated intravascular coagulation (DIC), and multi-organ failure. The hallmark lab finding of DIC is prolonged PT/PTT, low fibrinogen, elevated D-dimer, and microangiopathic hemolytic anemia with schistocytes.

Major Exotoxins You Must Know

Enzymes and Tissue Invasion

• Coagulase (S. aureus) — forms fibrin clot, walling off infection.
• Hyaluronidase (S. pyogenes, Clostridium) — 'spreading factor' hydrolyzes connective tissue ground substance.
• Streptokinase/staphylokinase — activate plasminogen, dissolving clots and aiding spread.
• Lecithinase (alpha-toxin) — C. perfringens membrane destruction.
• IgA protease — N. gonorrhoeae, N. meningitidis, H. influenzae, S. pneumoniae cleave secretory IgA.
• Urease — Proteus, H. pylori, Klebsiella; raises local pH (struvite stones in Proteus).
• DNase — S. pyogenes reduces pus viscosity.

The S. pyogenes – Rheumatic Fever Connection (PA-CAT Sample Item)

The PA-CAT Bulletin of Information, rev. 20240815, sample item describes a 13-year-old with sore throat, rash with pink rings and clear centers (erythema marginatum), and ASO antibodies. This is acute rheumatic fever (ARF) — a nonsuppurative sequela of Group A strep pharyngitis occurring 2–3 weeks after untreated infection. The mechanism is molecular mimicry:

• M protein on S. pyogenes shares epitopes with cardiac myosin and sarcolemmal membrane proteins.
• Anti-M antibodies cross-react with heart tissue, producing pancarditis (endocarditis, myocarditis, pericarditis).
• The mitral valve is most commonly damaged (mitral regurgitation acutely, mitral stenosis chronically).
• Cross-reactivity with joint synovium and basal ganglia explains polyarthritis and Sydenham chorea.

Modified Jones Criteria

Diagnosis requires evidence of preceding GAS infection (positive throat culture/NAAT or rising ASO/anti-DNase B titer) plus:

Two major OR one major + two minor establish the diagnosis. Primary prevention is prompt treatment of GAS pharyngitis with penicillin; secondary prevention is continuous prophylaxis (penicillin V or benzathine penicillin G monthly) for years after an ARF episode to prevent recurrence.

Contrast: Post-Streptococcal Glomerulonephritis (PSGN)

PSGN follows pharyngeal or skin GAS infection (1–3 weeks), occurs mainly in children, and is caused by immune complex deposition in glomeruli (subepithelial 'humps' on biopsy). Presents with edema, hypertension, hematuria (smoky urine), and low complement (C3). Unlike rheumatic fever, PSGN does not recur and is not prevented by penicillin prophylaxis.

Biofilms and Quorum Sensing

Biofilms are structured communities of bacteria encased in a self-produced extracellular matrix. They form on catheters, prosthetic joints, heart valves, and in CF airways (Pseudomonas alginate). Bacteria within biofilms are 10–1000× more antibiotic-resistant than planktonic cells due to slow growth, reduced penetration, and persister cells. Quorum sensing — density-dependent gene regulation via autoinducers (acyl-homoserine lactones in Gram-negatives, oligopeptides in Gram-positives) — coordinates virulence expression.

Antimicrobial Resistance Mechanisms

Extended-spectrum beta-lactamases (ESBLs) hydrolyze penicillins, cephalosporins, and monobactams (not carbapenems) — carbapenems are the treatment of choice. Carbapenemases (KPC, NDM-1) hydrolyze carbapenems and force the use of colistin or ceftazidime-avibactam.