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|標題:||NagZ-Dependent and NagZ-Independent Mechanisms for beta-Lactamase Expression in Stenotrophomonas maltophilia||作者:||Huang, Y.W.
|關鍵字:||pseudomonas-aeruginosa;enterobacter-cloacae;escherichia-coli;n-acetylglucosaminidase;level expression;signal molecule;bacterial-cell;induction;resistance;gene||Project:||Antimicrobial Agents and Chemotherapy||期刊/報告no：:||Antimicrobial Agents and Chemotherapy, Volume 56, Issue 4, Page(s) 1936-1941.||摘要:||
beta-N-Acetylglucosaminidase (NagZ), encoded by the nagZ gene, is a critical enzyme for basal-level ampC derepression (ampC expression in the absence of beta-lactam challenge) in ampD and dacB mutants of Pseudomonas aeruginosa. Three mutants with a phenotype of basal-level L1 and L2 beta-lactamase derepression in Stenotrophomonas maltophilia have been reported, including KJ Delta DI (ampD(I) mutant), KJ Delta mrcA (mrcA mutant), and KJ Delta DI Delta mrcA (ampD(I) and mrcA double mutant). In this study, nagZ of S. maltophilia was characterized, and its roles in basal-level beta-lactamase derepression, induced beta-lactamase activities, and beta-lactam resistance of KJ Delta DI, KJ Delta mrcA, and KJ Delta DI Delta mrcA were evaluated. Expression of the nagZ gene was constitutive and not regulated by AmpR, AmpD(I), AmpN, AmpG, PBP1a, and NagZ. Introduction of Delta nagZ into KJ Delta DI nearly abolished basal-level derepressed beta-lactamase activity; conversely, introduction of Delta nagZ into KJ Delta mrcA did not affect it. At least two activator ligands (ALs) are thus considered responsible for beta-lactamase expression in the S. maltophilia system, specifically, the NagZ-dependent (AL1,) and NagZ-independent (AL2) ligands responsible for the basal-level derepressed beta-lactamase activities of KJ Delta DI and KJ Delta mrcA, respectively. The contributions of AL1 and AL2 to the induced beta-lactamase activities may vary with the types of beta-lactams. nagZ inactivation did not affect aztreonam-, cefoxitin-, and carbenicillin-induced beta-lactamase activities, but it attenuated cefuroxime- and piperacillin-induced beta-lactamase activities. Introduction of Delta nagZ into KJ, KJ Delta DI, KJ Delta mrcA, and KJ Delta DI Delta mrcA did not significantly change the MICs of the beta-lactams tested except that the MICs of cefuroxime and piperacillin moderately decreased in strains KJ Delta Z and KJ Delta DI Delta Z (nagZ mutants).
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