title: Isoniazid resistance and the future of drug-resistant tuberculosis.
abstract: Bacterial chromosomal mutations that confer antibiotic resistance often have deleterious effects that impose costs on reproductive fitness. This observation has led to the generalization that in the absence of the selection pressure exerted through treatment, the frequency of resistance will decrease. This model implies that the prudent use of antibiotics will eventually result in a decline in the prevalence of drug resistance. Recent work, however, suggests that some resistance-conferring mutations may not significantly impair fitness and that others may be accompanied by compensatory mutations that restore the organisms' reproductive potential. Thus drug resistance, once introduced, may persist unless specific measures are implemented to target prevalent drug-resistant cases. Here we present ecological evidence to support the hypothesis that mutations at the 315 position of katG confer isoniazid resistance for Mycobacterium tuberculosis without diminishing virulence or transmissibility.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.forename: Megan B
authors.initials: MB
authors.lastname: Murray
mesh_terms: D001426:Bacterial Proteins; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D009154:Mutation / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010088:Oxidoreductases; D010544:Peroxidases; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010088:Oxidoreductases; D010544:Peroxidases; C076136:catalase HPI; C085257:InhA protein, Mycobacterium; D007538:Isoniazid