Role of efflux pumps in drug resistance in M. tuberculosis


Mandira Varma-Basil

University of Delhi, India

: Med Microbiol Rep

Abstract


Genomic mutations in drug targets have been identified as the major cause of drug resistance in M. tuberculosis. However, a section of isolates do not possess these mutations despite being drug resistant. Approximately 20 to 30% of clinical isoniazid (INH) resistant, 5% rifampicin (RIF) resistant and 40% Ethambutol (EMB) resistant M. tuberculosis isolates do not harbor mutations. Therefore, it is evident that other, more undefined mechanisms play a role in drug resistance. Analysis of genome sequences has shown that M. tuberculosis have multiple putative efflux pumps. However, the role of efflux pumps in intrinsic and acquired resistance has been neglected as a major cause for antibiotic resistance of M. tuberculosis and has only recently received attention. We evaluated the role of putative efflux pumps in providing resistance to INH, RIF and EMB in clinical isolates of M. tuberculosis. Isolates were also analysed for canonical mutations in katG, inhA, rpoB and embB306. Our study suggested a possible association of efflux pumps and resistance to RIF, INH and EMB. Although the mechanism behind efflux pumps overexpression and regulation is not clearly understood, it could be relevant to study mutations upstream or in the predicted promoter region of these genes to identify additional molecular markers for drug resistance.

Biography


Prof. Mandira Varma Basil is a Medical Microbiologist currently working at Vallabhbhai Patel chest Institute, Delhi, India where she is incharge of the Mycobacteriology unit . She obtained her MD in Microbiology from the University of Delhi and her DNB from the National Board of Examinations, Delhi, India. She is the recipient of the Department of Biotechnology (Government of India) Overseas Associateship and the Indian Council of Medical Research International Fellowship. Her main areas of interest include TB diagnosis, drug resistance in M. tuberculosis, molecular epidemiology of M. tuberculosis and non-Mycobacteria tuberculous. Dr. Varma-Basil has several publications and book chapters to her credit.

E-mail: mandirav2001@yahoo.com

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