The Alternative Sigma Factors SigE and SigB Are Involved in Tolerance and Persistence to Antitubercular Drugs

• Published in: Antimicrobial agents and chemotherapy 2017-12, Vol.61 (12)
• Main Authors: Pisu, Davide, Provvedi, Roberta, Espinosa, Dulce Mata, Payan, Jorge Barrios, Boldrin, Francesca, Palù, Giorgio, Hernandez-Pando, Rogelio, Manganelli, Riccardo
• Format: Article
• Language: English
• Subjects: Antitubercular Agents; Bacterial Proteins; Drug Tolerance; Ethambutol; Gene Expression Regulation, Bacterial; Mechanisms of Action: Physiological Effects; Mycobacterium tuberculosis; Sigma Factor
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01596-17

The emergence and spread of drug-resistant strains possibly threaten our ability to treat this disease in the future. Even though two new antitubercular drugs have recently been introduced, there is still the need to design new molecules whose mechanisms of action could reduce the length of treatment. We show that two alternative sigma factors of (SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long-duration drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug, is highly bactericidal for mutants missing either SigE or SigB. We suggest that molecules able to interfere with the activity of SigE or SigB not only could reduce virulence but also could boost the effect of other drugs by increasing the sensitivity of the organism and reducing the number of persisters able to escape killing.