2012年12月2日 訊 /生物谷BIOON/ --近日，刊登在近日國際雜志Antimicrobial Agents and Chemotherapy上的一篇研究報(bào)告“GES-18,， a new carbapenem-hydrolyzing GES-type β-lactamase from Pseudomonas aeruginosa that contains Ile80 and Ser170 residues.”中,，來自魯汶大學(xué)等處的研究者揭示了綠膿桿菌中發(fā)現(xiàn)的一種新型的碳青霉烯類抗生素的水解酶GES-18。
這種新型的抗生素水解酶是從一株臨床菌株中分離得到的,，研究者對一位來自比利時(shí),，患有下呼吸道感染的81歲老人身上分離到的臨床菌株。
研究者使用PCR測序技術(shù)對菌株進(jìn)行分析,，鑒別出了一種新型的GES突變體,，命名為GES-18，其不同于碳青霉烯類水解酶GES-5和GES-1,。進(jìn)行詳細(xì)的動力學(xué)分析后,，研究者Kurt M. Hoffmann說，GES-18和GES-5可以根據(jù)類似的動力學(xué)參數(shù)水解抗生素亞胺培南和頭孢西丁,。而GES-18相比GES-1,，在水解β內(nèi)酰胺酶抑制劑如克拉維酸鹽和三唑巴坦上,，表現(xiàn)出較低的敏感性,。
GES-18的結(jié)構(gòu)類似于GES-1和GES-2的水解結(jié)構(gòu)，而殘基Val80Ile和Gly170Ser可以引發(fā)其結(jié)構(gòu)更為精細(xì)的重排,，更值得注意的是,，水解水分子及Glu166殘基相比GES-1類似物來說可以輕松被移除。
總之研究者的動力學(xué)分析及晶體學(xué)結(jié)果揭示了,，GES-18可以通過Gly170Ser殘基的置換來區(qū)分其與GES-5的差別,。這對于深入研究細(xì)菌的耐藥性非常關(guān)鍵。（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.
