通过将69位的甲硫氨酸替换为异亮氨酸或缬氨酸构建的突变型SHV-5β-内酰胺酶的特性
Properties of mutant SHV-5 beta-lactamases constructed by substitution of isoleucine or valine for methionine at position 69.
作者信息
Giakkoupi P, Miriagou V, Gazouli M, Tzelepi E, Legakis N J, Tzouvelekis L S
机构信息
Department of Bacteriology, Hellenic Pasteur Institute, Athens, Greece.
出版信息
Antimicrob Agents Chemother. 1998 May;42(5):1281-3. doi: 10.1128/AAC.42.5.1281.
Abstract
The effect of replacement of Met-69 by Ile or Val on the properties of the extended-spectrum beta-lactamase SHV-5 was studied. Mutant enzymes were constructed by site-specific mutagenesis and expressed under isogenic conditions in Escherichia coli DH5alpha cells. Compared with SHV-5, the mutant beta-lactamases conferred lower levels of beta-lactam resistance and were less efficient in hydrolyzing ampicillin, cephalothin, and cefotaxime. The substitutions rendered SHV-5 less susceptible to inhibition by clavulanate, sulbactam, and tazobactam; however, the MICs of penicillin-inhibitor combinations remained similar, suggesting an attenuation of penicillinase activity.
摘要
研究了将甲硫氨酸-69替换为异亮氨酸或缬氨酸对超广谱β-内酰胺酶SHV-5性质的影响。通过定点诱变构建突变酶，并在同基因条件下在大肠杆菌DH5α细胞中表达。与SHV-5相比，突变型β-内酰胺酶赋予的β-内酰胺抗性水平较低，并且在水解氨苄西林、头孢噻吩和头孢噻肟方面效率较低。这些取代使SHV-5对克拉维酸、舒巴坦和他唑巴坦的抑制作用更不敏感；然而，青霉素抑制剂组合的最低抑菌浓度保持相似，表明青霉素酶活性减弱。
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