Mycobacterium tuberculosis
One-Sentence Definition
Mycobacterium tuberculosis is a slow-growing, acid-fast bacillus with a waxy mycolic-acid cell wall that causes tuberculosis, still among the leading infectious causes of death worldwide.
Taxonomy & Morphology
- Acid-fast bacillus; not classifiable by Gram Stain — use Acid-Fast Stain (Ziehl-Neelsen or auramine fluorescence)
- Cell wall rich in mycolic acids, arabinogalactan, and lipoarabinomannan → acid fastness, low permeability, resistance to drying and disinfectants
- Generation time ~15–20 hours; solid culture takes up to 6–8 weeks
Virulence Highlights
- Survives inside macrophages by blocking phagosome–lysosome fusion
- ESX-1 (RD1) secretion system → phagosomal escape and tissue damage
- Cord factor (trehalose dimycolate) → granuloma formation
- Immune response causes the pathology: caseating granuloma
Clinical Syndromes
- Latent TB infection — contained, non-infectious, positive immune test, no disease
- Pulmonary TB — chronic cough, weight loss, night sweats, haemoptysis; upper-lobe cavitation on reactivation
- Extrapulmonary — lymphadenitis, pleural, TB meningitis, spinal (Pott disease), miliary/disseminated
- Risk of progression rises sharply with HIV, malnutrition, diabetes, TNF inhibitors
Diagnosis
- Molecular first: Xpert MTB/RIF and successors detect M. tuberculosis and rifampicin resistance in hours (PCR)
- Smear microscopy (Acid-Fast Stain) — fast, insensitive, still widely used
- Culture on Löwenstein-Jensen or liquid MGIT — the reference standard, but slow
- Latent infection: tuberculin skin test or interferon-γ release assay — these detect exposure, not active disease
- Whole-Genome Sequencing increasingly used for full resistance prediction and transmission tracing
Treatment & AMR
- Standard regimen: rifampicin, isoniazid, pyrazinamide, ethambutol — multi-drug and long-course, specifically to prevent resistance emerging
- MDR-TB: resistant to rifampicin and isoniazid. XDR-TB: plus fluoroquinolone and another key agent
- Resistance is chromosomal point mutation, not plasmid-borne: rpoB (rifampicin), katG/inhA (isoniazid), gyrA (fluoroquinolones), pncA (pyrazinamide)
- This makes TB the strongest case for Genotype to Phenotype Prediction — mechanisms are few, catalogued, and WHO-endorsed for genomic reporting
Public Health
- Airborne precautions (Infection Prevention and Control); contact tracing; directly observed therapy programmes
- BCG protects against severe childhood TB but poorly against adult pulmonary disease (Vaccination)
History
- Robert Koch identified the bacillus in 1882 — the demonstration case for Koch’s Postulates
Related MOCs
- MOC - Bacteriology · MOC - Clinical Microbiology · MOC - Antimicrobial Resistance (AMR) · MOC - Public Health & Epidemiology
Active Recall Questions
- Why does the Gram stain fail for mycobacteria?
- Why is TB treated with four drugs for months?
- Why is genomic resistance prediction unusually reliable in TB?