000151262 001__ 151262
000151262 005__ 20181203021958.0
000151262 022__ $$a0950-382X
000151262 02470 $$2PMID$$a11401695
000151262 0247_ $$2doi$$a10.1046/j.1365-2958.2001.02427.x
000151262 037__ $$aARTICLE
000151262 245__ $$aRegulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis
000151262 269__ $$a2001
000151262 260__ $$c2001
000151262 336__ $$aJournal Articles
000151262 520__ $$aMycobacterium tuberculosis has two genes for ferric uptake regulator orthologues, one of which, furA, is situated immediately upstream of katG encoding catalase-peroxidase, a major virulence factor that also activates the prodrug isoniazid. This association suggested that furA might regulate katG and other genes involved in pathogenesis. Transcript mapping showed katG to be expressed from a strong promoter, with consensus -10 and -35 elements, preceding furA. No promoter activity was demonstrated downstream of the furA start codon, using different gene reporter systems, indicating that furA and katG are co-transcribed from a common regulatory region. The respective roles of these two genes in the isoniazid susceptibility and virulence of M. tuberculosis were assessed by combinatorial complementation of a Delta(furA-katG) strain that is heavily attenuated in a mouse model of tuberculosis. In the absence of furA, katG was upregulated, cells became hypersensitive to isoniazid, and full virulence was restored, indicating that furA regulates the transcription of both genes. When furA alone was introduced into the Delta(furA-katG) mutant, survival in mouse lungs was moderately increased, suggesting that FurA could regulate genes, other than katG, that are involved in pathogenesis. These do not include the oxidative stress genes ahpC and sodA, or those for siderophore production.
000151262 700__ $$aPym, A S
000151262 700__ $$aDomenech, P
000151262 700__ $$aHonoré, N
000151262 700__ $$aSong, J
000151262 700__ $$aDeretic, V
000151262 700__ $$g177247$$aCole, S T$$0243892
000151262 773__ $$j40$$tMolecular microbiology$$k4$$q879-89
000151262 909C0 $$xU11742$$0252302$$pUPCOL
000151262 909CO $$pSV$$particle$$ooai:infoscience.tind.io:151262
000151262 937__ $$aEPFL-ARTICLE-151262
000151262 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000151262 980__ $$aARTICLE