Mycobacteria Overview and Characteristics

Mycobacteria Overview

• Mycobacteria are slow-growing, aerobic, facultative intracellular bacteria with a lipid-rich cell wall, which makes them acid-fast.
• Important examples include M. tuberculosis, M. bovis, M. leprae, and others.

Shared Mycobacterial Properties

• Slow-growing bacteria. '
• Aerobic, facultative intracellular rods (bacteria).
• Lipid-rich cell wall causing acid-fast staining.

Mycobacteria Associated with Human Disease

General Characteristics

• Rod-shaped, aerobic bacilli.
• Non-spore-forming.
• Non-motile.
• Cell wall rich in lipids (making them acid-fast).
• Very slow-growing.

Mycobacterial Cell Wall Structure

• Complex lipid composition (>60% of the cell wall).
• Mycolic acids: Strong hydrophobic molecules forming a lipid shell, affecting cell surface permeability.
• Cord factor: Toxic to mammalian cells; inhibits polymorphonuclear leukocyte (PMN) migration.
• Wax-D: Component of the cell envelope.

Mycobacterial Cell Wall Implications

• High lipid concentration impedes staining and dye penetration.
• Creates resistance to many antibiotics.
• Resistance to acidic and alkaline compounds.
• Resistance to lysis by complement deposition.
• Resistance to killing by oxidative mechanisms; survival within macrophages.

Modes of Tuberculosis Infection

• Inhalation (Droplet Infection): Person-to-person via aerosols, causing pulmonary TB.
• Ingestion (Milk): Infected cattle; causes intestinal TB.
• Contamination (Abrasion): Laboratory exposure; skin infection.

Predisposing Factors for Tuberculosis Infection

• HIV infection (highest risk factor).
• Overcrowding.
• Poor nutrition.
• IV drug abuse.
• Alcoholism.

Tuberculosis Pathogenesis

• Initial Infection: Inhaled mycobacteria are engulfed by alveolar macrophages; replicate intracellularly. Cell wall prevents destruction in lysosomes.
• Macrophage Interactions: Attraction of other macrophages to destroy infected ones; releases mycobacteria capable of bloodstream spread.
• Tubercle Formation: Granulomatous lesions (tubercles) form around initial infection sites. Activated macrophages & lymphocytes aggregate.
• Caseous Granulomas: Large tubercles have a central necrotic region, surrounded by fibrin, halting further spread.
• Dormant Mycobacteria: Mycobacteria remain viable and dormant within tubercles, capable of release later.
• T-cell Response: Host delayed-type hypersensitivity (DTH) response, essential for infection control, but can cause tissue damage and fibrosis.

Post-Primary Tuberculosis

• Reactivation of dormant tubercles or exogenous infection.
• May occur spontaneously or after illnesses weakening the host's immune response.
• Primarily affects upper lung lobes
• Similar granuloma formation with necrotic areas (tuberculomas) causing tissue damage.
• Tissue liquefaction by proteases; TNF and other mediators lead to wasting and fever.
• Cavity formation: Organisms released into sputum; infectious person.
• Secondary lesions can occur in various organs (e.g., genitourinary, bones, joints, lymph nodes, peritoneum) due to miliary TB.

Factors Influencing Tuberculosis Progression

• Mycobacterial strain.
• Prior exposure.
• Vaccination.
• Infectious dose.
• Host immune status.

Mycobacterial Virulence Mechanisms

• Direct/Indirect entry to macrophages via receptors.
• Intracellular growth avoids antibodies/complement.
• Inhibition of phagosome-lysosome fusion via secreted proteins.
• Survival in macrophages (phagosome, escaping phagosome).
• Interference with reactive oxygen (protective compounds).

Mycobacterial Virulence Factors (cont.)

• High lipid content: Impairs antimicrobial action, osmotic lysis, and lysozyme attack.
• Cord factor: Toxic to cells, inhibits PMN migration.

Clinical Course of Tuberculosis

• Primary Pulmonary Tuberculosis: Active disease in 5-10% of cases within 2 years.

• Foci in the lung following inhalation.

• DTH response limits proliferation in mid-lower lungs, forming tubercles.

• Manifestations: Weight loss, night sweats, fever, cough.

• Non-specific: malaise, weight loss, cough, night sweats, hemoptysis.

• Active disease: pneumonia, abscesses in lungs, cavitation.

• Calcification of lesions: Ghon complexes.

• Secondary Pulmonary Tuberculosis: Reactivation or re-infection; common in immunocompromised patients. Common in the upper lobe of the lung.

• Fibrocaseous cavity lesions near the apex of the upper lobe

• Extra-pulmonary Tuberculosis: Hematogenous spread (e.g., lymph nodes, pleura, genitourinary tract, CNS) leads to tissue damage.

• Symptoms: Chest pain (pleurisy), swollen lymph nodes, joint pain (arthritis), spinal deformity (Pott's disease), headache, fever, stiff neck, mental confusion (meningitis)

Tuberculosis Diagnosis

• Physical examination (lymph node swelling, lung sounds).
• Skin tests.
• Blood and sputum tests.
• Imaging (e.g., chest CT scan).
• Pleural fluid analysis.
• Interferon-gamma release assays (IGRAs).

Tuberculosis Diagnostic Procedures & Tests

• Tuberculin skin test (TST): Detects immune response to TB.
• Chest CT scan: Confirms pulmonary TB.
• Sputum culture test: Identifies the bacteria.
• Interferon-gamma release assay (IGRA): Blood test for active/latent TB.
• Sputum microscopy (acid-fast bacilli)

Tuberculin Skin Test (TST)

• Diagnosis of TB infection (not disease).
• Injection into forearm skin; reaction assessed in 48-72 hours.
• Reaction size indicates infection status

Tuberculosis Treatment

• Multidrug therapy (4 antimicrobial agents) for 6-9 months.
• RIPE regimen (Rifampin, Isoniazid, Pyrazinamide, Ethambutol).
• Intensive phase (2 months); continuation phase (4-7 months).

Tuberculosis Prevention

• Improved social conditions.
• Case detection & treatment.
• Contact tracing.
• Treatment of infected/diseased contacts.
• Immunization (BCG).

Multi-Drug Resistant Tuberculosis (MDR TB) and Extensively Drug-Resistant Tuberculosis (XDR TB)

• Resistance arises from mismanaged/abused drug use.
• Incomplete treatment courses, inappropriate treatment from healthcare providers, drug supply issues, and quality of drugs contribute to resistance.
• XDR TB: Resistance to first-line & some second-line drugs.

MDR & XDR TB Risk Factors

• Patients not adhering to their treatment.
• Reactivation of prior tuberculosis in immunocompromised patients. including HIV patients at high risk

Summary

• Mycobacterial infections cause critical diseases like tuberculosis.
• Virulence factors, like complex lipids in the cell wall, hamper treatments.
• Diagnosis involves physical examination, skin tests & sputum analysis; imaging.
• Treatment requires multi-drug regimens.
• Prevention focuses on improving social conditions & treatment adherence.

This quiz covers the essential properties and classification of mycobacteria, including their slow-growing nature and acid-fast characteristics. You'll also explore various mycobacterial species associated with human diseases and their environmental reservoirs. Test your knowledge on the different types of mycobacteria and their implications for human health.