Graduate Institute of Microbiology and Public Health, National Chung-Hsing University, Taichung, Taiwan.
Antimicrob Agents Chemother. 2012 Apr;56(4):1936-41. doi: 10.1128/AAC.05645-11. Epub 2012 Jan 17.
β-N-Acetylglucosaminidase (NagZ), encoded by the nagZ gene, is a critical enzyme for basal-level ampC derepression (ampC expression in the absence of β-lactam challenge) in ampD and dacB mutants of Pseudomonas aeruginosa. Three mutants with a phenotype of basal-level L1 and L2 β-lactamase derepression in Stenotrophomonas maltophilia have been reported, including KJΔDI (ampD(I) mutant), KJΔmrcA (mrcA mutant), and KJΔDIΔmrcA (ampD(I) and mrcA double mutant). In this study, nagZ of S. maltophilia was characterized, and its roles in basal-level β-lactamase derepression, induced β-lactamase activities, and β-lactam resistance of KJΔDI, KJΔmrcA, and KJΔDIΔmrcA were evaluated. Expression of the nagZ gene was constitutive and not regulated by AmpR, AmpD(I), AmpN, AmpG, PBP1a, and NagZ. Introduction of ΔnagZ into KJΔDI nearly abolished basal-level derepressed β-lactamase activity; conversely, introduction of ΔnagZ into KJΔmrcA did not affect it. At least two activator ligands (ALs) are thus considered responsible for β-lactamase expression in the S. maltophilia system, specifically, the NagZ-dependent (AL1) and NagZ-independent (AL2) ligands responsible for the basal-level derepressed β-lactamase activities of KJΔDI and KJΔmrcA, respectively. The contributions of AL1 and AL2 to the induced β-lactamase activities may vary with the types of β-lactams. nagZ inactivation did not affect aztreonam-, cefoxitin-, and carbenicillin-induced β-lactamase activities, but it attenuated cefuroxime- and piperacillin-induced β-lactamase activities. Introduction of ΔnagZ into KJ, KJΔDI, KJΔmrcA, and KJΔDIΔmrcA did not significantly change the MICs of the β-lactams tested except that the MICs of cefuroxime and piperacillin moderately decreased in strains KJΔZ and KJΔDIΔZ (nagZ mutants).
β-N-乙酰氨基葡萄糖苷酶（NagZ）由 nagZ 基因编码，是铜绿假单胞菌 ampD 和 dacB 突变体中基础水平 ampC 去阻遏（无β-内酰胺挑战时的 ampC 表达）的关键酶。已报道有 3 种嗜麦芽寡养单胞菌具有基础水平 L1 和 L2 内酰胺酶去阻遏表型的突变体，包括 KJΔDI（ampD(I)突变体）、KJΔmrcA（mrcA 突变体）和 KJΔDIΔmrcA（ampD(I)和 mrcA 双突变体）。本研究对嗜麦芽寡养单胞菌的 nagZ 进行了表征，并评估了其在 KJΔDI、KJΔmrcA 和 KJΔDIΔmrcA 中的基础水平β-内酰胺酶去阻遏、诱导β-内酰胺酶活性和β-内酰胺耐药性中的作用。nagZ 基因的表达是组成型的，不受 AmpR、AmpD(I)、AmpN、AmpG、PBP1a 和 NagZ 的调控。将ΔnagZ 导入 KJΔDI 中几乎完全消除了基础水平去阻遏的β-内酰胺酶活性；相反，将ΔnagZ 导入 KJΔmrcA 中并不影响其活性。因此，至少有两种激活配体（AL）被认为负责嗜麦芽寡养单胞菌系统中的β-内酰胺酶表达，具体而言，NagZ 依赖性（AL1）和 NagZ 非依赖性（AL2）配体分别负责 KJΔDI 和 KJΔmrcA 的基础水平去阻遏的β-内酰胺酶活性。AL1 和 AL2 对诱导β-内酰胺酶活性的贡献可能因β-内酰胺的类型而异。nagZ 失活不影响氨曲南、头孢西丁和羧苄西林诱导的β-内酰胺酶活性，但会减弱头孢呋辛和哌拉西林诱导的β-内酰胺酶活性。将ΔnagZ 导入 KJ、KJΔDI、KJΔmrcA 和 KJΔDIΔmrcA 中除了菌株 KJΔZ 和 KJΔDIΔZ（nagZ 突变体）中头孢呋辛和哌拉西林的 MIC 适度降低外，对所测试的β-内酰胺的 MIC 没有显著影响。
