From the Guidelines
Mycobacterium tuberculosis employs several key virulence factors, including the waxy cell wall, ESX secretion systems, lipoarabinomannan, cord factor, protein kinase G, catalase-peroxidase, and iron acquisition systems, to establish and maintain infection. These virulence factors work together to help the bacterium evade immune clearance, survive within macrophages, and establish persistent infection, making tuberculosis particularly difficult to treat and requiring lengthy antibiotic regimens. The role of the organism itself in transmission is only beginning to be understood, with genetic variability believed to affect the capability of M. tuberculosis strains to be transmitted or to cause disease once transmitted, or both 1. The M. tuberculosis W-strain family is a group of clonally related multidrug-resistant organisms that caused nosocomial outbreaks involving HIV-infected persons, and is believed to have evolved from a single strain of M. tuberculosis that developed resistance-conferring mutations in multiple genes 1. Some key points about Mycobacterium virulence factors include:
- The waxy cell wall containing mycolic acids provides protection against host defenses and antibiotics while also triggering inflammatory responses
- The ESX secretion systems, particularly ESX-1, deliver effector proteins that disrupt phagosome maturation and allow bacterial escape into the cytosol
- Lipoarabinomannan (LAM) inhibits phagosome-lysosome fusion and modulates immune signaling
- Cord factor (trehalose dimycolate) contributes to granuloma formation and inflammatory responses
- Protein kinase G prevents phagosome acidification, while catalase-peroxidase (KatG) neutralizes reactive oxygen species
- Iron acquisition systems like mycobactins enable survival in low-iron environments within the host
- Mycobacterium also produces various enzymes that detoxify antimicrobial compounds and employs dormancy regulators that facilitate latent infection by slowing metabolism during stress 1.
From the Research
Mycobacterium Virulence Factors
- Mycobacterium tuberculosis strains resistant to at least two of the most effective anti-tuberculosis drugs (i.e., isoniazid and rifampicin) cause multi-drug resistant tuberculosis (MDR-TB) 2
- The emergence and spread of MDR-TB can be favored by poor implementation of the DOTS strategy, shortage or poor quality of anti-tuberculosis drugs, and poor therapeutic adherence of patients to prescribed regimens 2
- Mechanisms of action and resistance of M. tuberculosis to isoniazid and rifampin are crucial in understanding MDR-TB, with resistance to rifampicin mediated by mutations in the rpoB gene and resistance to isoniazid mediated by mutations in katG and other genes 3, 4
- Molecular diagnostic testing, including line probe assays, molecular beacon-based real-time polymerase chain reaction, and pyrosequencing, can be used to detect drug susceptibility in M. tuberculosis, but results must be interpreted within the clinical context of each patient 3
Atypical Mycobacteria
- Atypical or nontuberculous mycobacteria (NTM) can cause a range of diseases, including pulmonary, soft-tissue, and disseminated infections, and treatment is challenging due to variability in bacterial susceptibility profiles and lack of evidence-based guidelines 5
- New treatment approaches are needed for NTM disease, including less conventional therapeutics such as antimicrobial peptides, bacteriophages, iron chelators, and host-directed therapies 5
Diagnostic Testing
- The fully automated BACTEC MGIT 960 system can be used for testing susceptibility of M. tuberculosis to pyrazinamide, streptomycin, isoniazid, rifampin, and ethambutol, with excellent performance but some discrepancies compared to the radiometric BACTEC 460TB system 6
- The BACTEC MGIT 960 system can represent a valid alternative to the BACTEC 460TB for M. tuberculosis susceptibility testing, but contamination of tests needs to be improved 6