Isoniazid resistance without a loss of fitnessin Mycobacterium tuberculosis

摘要

The emergence of multi- and extensively drug-resistant tuberculosis (mDR-TB and XDR-TB,respectively) has intensified the critical public health implications of this global disease. Thefitness of Mycobacterium tuberculosis (M.tb.) strains exhibiting mDR and XDR phenotypes is offundamental importance in predicting whether the mDR-/XDR-TB epidemic will be sustainedacross the human population. Here we describe a potential mechanism of M.tb. resistance tothe TB drug isoniazid (InH) conferred by loss of a sigma factor, sigI. We demonstrate thatthe gain of InH resistance in the M.tb. UsigI mutant might not diminish the organism’s fitnessfor causing disease. These findings have significant implications when considering the abilityof drug-resistant M.tb. strains to initiate untreatable TB epidemics, as it is possible that loss oralteration of sigI function could have a role in the generation of mDR and XDR M.tb. strains ofsuitable fitness to spread in a community setting.