Molecular characterization of a β-lactamase gene, blaGIM-1, encoding a new subclass of metallo-β-lactamase
Molecular characterization of a β-lactamase gene, blaGIM-1, encoding a new subclass of metallo-β-lactamase
复制标题
DOI：
10.1128/aac.48.12.4654-4661.2004
复制
发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Walsh, TR
中科院分区：
文献类型：
--
作者：
Castanheira, M;Toleman, MA;Walsh, TR
作为2002年SENTRY抗菌药物监测计划的一部分，检测到5株多重耐药铜绿假单胞菌临床分离株具有金属β-内酰胺酶（MbetaL）活性。分离株来自位于德国杜塞尔多夫的医疗中心的不同患者。扩增整合酶和aacA 4基因盒之间的区域，分离抗性决定簇。测序结果显示了一个新的MbetaL基因，命名为bla（GIM-1）。进一步的分析表明，GIM-1，包括250个氨基酸，pI值为5.4，其一级序列与IMP，Vim和SPM-1酶的一级序列分别相差39 - 43%，28 - 31%和28%。该酶在MbetaL家族的主要共有序列（HXHXD）内具有独特的氨基酸。动力学分析表明，GIM-1对任何底物都没有明显的偏好，并且不水解阿洛西林、氨曲南和丝氨酸-β-内酰胺酶抑制剂。bla（GIM-1）存在于22-kb的不可转移质粒上。新的MOL基因嵌入在6-kb 1类整合子In 77的第一个位置，具有独特的特征，包括MbetaL基因下游的aacA 4盒，其似乎被bla（GIM-1）截短。aacA 4之后是aadA 1基因盒，其被IS 1394的拷贝中断。该整合子还在3 '-CS区之前携带苯唑西林酶基因bla（OXA-2）。GIM-1似乎是一种独特的MbetaL，其位于不同的整合子结构中，并且代表待表征的移动的MbetaL酶的第四亚类。
As part of the SENTRY Antimicrobial Surveillance Program in 2002, five multidrug-resistant Pseudomonas aeruginosa clinical isolates were detected with metallo-beta-lactamase (MbetaL) activity. The isolates were recovered from different patients in a medical center located in Dusseldorf, Germany. The resistant determinant was isolated amplifying the region between the integrase and the aacA4 gene cassette. Sequencing revealed a novel MbetaL gene, designated bla(GIM-1). Additional analysis showed that GIM-1, comprising 250 amino acids and with a pI value of 5.4, differs in its primary sequence from that described for IMP, VIM, and SPM-1 enzymes by 39 to 43%, 28 to 31%, and 28%, respectively. The enzyme possesses unique amino acids within the major consensus sequence (HXHXD) of the MbetaL family. Kinetics analysis revealed that GIM-1 has no clear preference for any substrate and did not hydrolyze azlocillin, aztreonam, and the serine-beta-lactamase inhibitors. bla(GIM-1) was found on a 22-kb nontransferable plasmid. The new MOL gene was embedded in the first position of a 6-kb class 1 integron, In77, with distinct features, including an aacA4 cassette downstream of the MbetaL gene that appeared to be truncated with bla(GIM-1). The aacA4 was followed by an aadA1 gene cassette that was interrupted by a copy of the IS1394. This integron also carried an oxacillinase gene, bla(OXA-2), before the 3'-CS region. GIM-1 appears to be a unique MbetaL, which is located in a distinct integron structure, and represents the fourth subclass of mobile MbetaL enzymes to be characterized.