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Identification of novel metronidazole-inducible genes in Mycobacterium smegmatis using a customized amplification library

Kim, Su-Young, Shin, Sung Jae, Song, Chang-Hwa, Jo, Eun-Kyeong, Kim, Hwa-Jung, Park, Jeong-Kyu
FEMS microbiology letters 2008 v.282 no.2 pp. 282-289
Mycobacterium smegmatis, anaerobic conditions, antibiotic resistance, bacteria, cell walls, dormancy, drugs, gene expression regulation, genes, methyltransferases, metronidazole, mutants, mutation, permeability, transporters
The incidence of antibiotic resistance in pathogenic bacteria is rising. Bacterial resistance may be a natural defense of organisms, or it may result from spontaneous mutations or the acquisition of exogenous resistance genes. We grew spontaneous metronidazole-resistant Mycobacterium smegmatis mutants on solid medium cultures and employed differential expression using a customized amplification library to analyze the global gene profiles of metronidazole-resistant mutants under hypoxic conditions. In total, 66 genes involved in metronidazole resistance were identified and functionally characterized using the gene role category of M. smegmatis. Overall, genes associated with cell wall synthesis, such as methyltransferase and glycosyltransferase, and genes encoding drug transporters were highly expressed. The genes may be involved in the natural drug resistance of mycobacteria by increasing mycobacterial cell wall permeability and the efflux pumps of active drugs. In addition, the genes may play a role in dormancy. The genes identified in this study may lead to a better understanding of the mechanisms of metronidazole resistance during dormancy.