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A complex regulatory network controlling intrinsic multidrug resistance in M ycobacterium smegmatis
Author(s) -
Bowman Joshua,
Ghosh Pallavi
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12448
Subject(s) - mycobacterium smegmatis , biology , regulon , efflux , serine , gene , mutant , biochemistry , phosphorylation , genetics , microbiology and biotechnology , mycobacterium tuberculosis , medicine , tuberculosis , pathology
Summary Mycobacteria are intrinsically resistant to a variety of stresses including many antibiotics. Although a number of pathways have been described to account for the observed resistances, the mechanisms that control the expression of genes required in these processes remain poorly defined. Here we report the role of a predicted anti‐sigma factor, MSMEG _6129 and a predicted eukaryotic like serine/threonine protein kinase, MSMEG _5437, in the intrinsic resistance of M ycobacterium smegmatis to a variety of stresses including the genotoxic agent mitomycin C , hydrogen peroxide and at least four different antibiotics – isoniazid, chloramphenicol, erythromycin and tetracycline. We show that MSMEG _5437 influences the phosphorylation state of MSMEG _6129. Further, MSMEG _6129 controls the expression of a plethora of genes including efflux pumps, ABC transporters, catalases and transcription factors, either directly or via regulators like WhiB7, which account for the observed multi‐drug resistance phenotypes. MSMEG _6129 in turn phosphorylates a contiguously located putative anti‐anti‐sigma factor, MSMEG _6127. We therefore propose that MSMEG _5437, MSMEG _6129 and MSMEG _6127 are components of a master regulatory network, upstream of whiB7 , that controls the activity of one or more of the 28 sigma factors in M . smegmatis . Together, this network controls the expression of a regulon required for resistance to several unrelated antibiotics.