title: Differential expression of efflux pump genes of Mycobacterium tuberculosis in response to varied subinhibitory concentrations of antituberculosis agents.
abstract: Several reports have elaborated on the role of efflux pumps in drug resistance in Mycobacterium tuberculosis by analysing the mRNA expression profiles. However, there is no uniformity in the subinhibitory concentrations of drugs chosen in these studies. Some investigators studied the expression of efflux pumps under a drug concentration of 1/2 minimum inhibitory concentration (MIC), while others used 1/3, 1/4 or 1/8MIC. The present study was planned to understand the effect of different concentrations of antituberculosis drugs on the expression of efflux pump genes. Log phase culture of the laboratory strain M. tuberculosis H37Rv was exposed to rifampicin (RIF), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) at different drug concentrations (1/2MIC, 1/3MIC and 1/4MIC). The expression of 10 putative efflux pump genes was studied using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We observed an optimal expression of efflux pumps at higher concentrations of INH; and at lower concentrations of RIF and EMB. However, in the presence of SM, a decreased expression of efflux genes with increasing concentrations of the drug was confounded by a significant reduction in Colony Forming Units (CFU).
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors: Kushal
authors: K
authors: Garima
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors: Rakesh
authors: R
authors: Pathak
authors: Department of Biochemistry, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors: Rashmi
authors: R
authors: Tandon
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors: Nisha
authors: N
authors: Rathor
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors: Rajesh
authors: R
authors: Sinha
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors: Mridula
authors: M
authors: Bose
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. Electronic address: mandirav@rediffmail.com.
authors: Mandira
authors: M
authors: Varma-Basil
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D013379:Substrate Specificity; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000995:Antitubercular Agents; D026901:Membrane Transport Proteins
keywords: Antituberculosis agents; Efflux pumps; Mycobacterium tuberculosis