The alternative sigma factors SigE and SigB are involved in tolerance and persistence to antitubercular drugs [PublishAheadOfPrint]

Emergence and spread of drug resistant Mycobacterium tuberculosis strains threatens our ability the possibility to treat this disease in the future. Even if two new antitubercular drugs were recently introduced, there is still the need to design new molecules whose mechanism of action could reduce treatment length. We showed that two alternative sigma factors of M. tuberculosis (SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug is highly bactericidal for M. tuberculosis mutants missing either SigE or SigB. We suggest that developing molecules able to interfere with their activity could not only reduce M. tuberculosis virulence in vivo, but also boost the effect of other drugs by increasing its sensitivity and reducing the number of persisters able to escape killing.

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