2012年12月2日 讯 /生物谷BIOON/ --近日，刊登在近日国际杂志Antimicrobial Agents and Chemotherapy上的一篇研究报告“GES-18， a new carbapenem-hydrolyzing GES-type β-lactamase from Pseudomonas aeruginosa that contains Ile80 and Ser170 residues.”中，来自鲁汶大学等处的研究者揭示了绿脓杆菌中发现的一种新型的碳青霉烯类抗生素的水解酶GES-18。
这种新型的抗生素水解酶是从一株临床菌株中分离得到的，研究者对一位来自比利时，患有下呼吸道感染的81岁老人身上分离到的临床菌株。
研究者使用PCR测序技术对菌株进行分析，鉴别出了一种新型的GES突变体，命名为GES-18，其不同于碳青霉烯类水解酶GES-5和GES-1。进行详细的动力学分析后，研究者Kurt M. Hoffmann说，GES-18和GES-5可以根据类似的动力学参数水解抗生素亚胺培南和头孢西丁。而GES-18相比GES-1，在水解β内酰胺酶抑制剂如克拉维酸盐和三唑巴坦上，表现出较低的敏感性。
GES-18的结构类似于GES-1和GES-2的水解结构，而残基Val80Ile和Gly170Ser可以引发其结构更为精细的重排，更值得注意的是，水解水分子及Glu166残基相比GES-1类似物来说可以轻松被移除。
总之研究者的动力学分析及晶体学结果揭示了，GES-18可以通过Gly170Ser残基的置换来区分其与GES-5的差别。这对于深入研究细菌的耐药性非常关键。（生物谷Bioon.com）
doi:10.1128/AAC.01784-12
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GES-18, a new carbapenem-hydrolyzing GES-type β-lactamase from Pseudomonas aeruginosa that contains Ile80 and Ser170 residues.
Carine Bebrone1,§, Pierre Bogaerts2, Heinrich Delbrück1, Sandra Bennink1, Michaël B. Kupper1, Roberta Rezende de Castro2, Youri Glupczynski2 and Kurt M. Hoffmann1
A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR-sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.
