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[Resistance to antituberculous drugs]
N Veziris1, E Cambau, W Sougakoff
1Laboratoire de bactériologie-Hygiène, CHU Pitié-Salpêtrière, Assistance-publique-Hôpitaux-de-Paris, 75651 Paris cedex 13, France. veziris@chups.jussieu.fr
Summary
Tuberculosis-causing mycobacteria develop antibiotic resistance through genetic mutations affecting drug targets or activators. Understanding these mechanisms is crucial for combating drug-resistant tuberculosis.
Area of Science:
- Microbiology
- Genetics
- Pharmacology
Context:
- Tuberculosis (TB) is caused by Mycobacterium species, which exhibit limited susceptibility to antibiotics.
- Antibiotic resistance in mycobacteria emerges rapidly upon drug exposure.
- Understanding resistance mechanisms is key to developing effective TB treatments.
Purpose:
- To investigate the genetic mechanisms underlying acquired antibiotic resistance in mycobacteria.
- To elucidate the mode of action for key antitubercular drugs.
- To analyze the prevalence of multidrug resistance in France.
Summary:
- Mycobacterium tuberculosis resistance to specific antibiotics like isoniazid, pyrazinamide, ethionamide, and ethambutol arises from mutations in genes encoding drug-activator enzymes (e.g., KatG, PncA) or drug targets (e.g., InhA, EmbB).
- These drugs are mycobacteria-specific, inhibiting mycolic acid synthesis essential for the bacterial cell wall.
- Resistance mechanisms for rifamycins, aminoglycosides, and quinolones are conserved between mycobacteria and other bacteria.
- No plasmids or resistance transposons have been identified in M. tuberculosis.
Impact:
- Advances in understanding drug action and resistance mechanisms in TB.
- Development of rapid diagnostic tests, such as DNA chips, for detecting multiple drug resistances.
- Current French data show 0.5% multidrug resistance, 9% primary resistance, and 16% secondary resistance to antitubercular drugs.