Novel Chimeric β-Lactamase CTX-M-64, a Hybrid of CTX-M-15-Like and CTX-M-14 β-Lactamases, Found in a Shigella sonnei Strain Resistant to Various Oxyimino-Cephalosporins, Including Ceftazidime
Novel Chimeric β-Lactamase CTX-M-64, a Hybrid of CTX-M-15-Like and CTX-M-14 β-Lactamases, Found in a Shigella sonnei Strain Resistant to Various Oxyimino-Cephalosporins, Including Ceftazidime
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DOI：
10.1128/aac.00227-08
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发表时间：
2009-01-01
影响因子：
4.9
通讯作者：
Arakawa, Yoshichika
中科院分区：
文献类型：
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作者：
Nagano, Yukiko;Nagano, Noriyuki;Arakawa, Yoshichika
质粒介导的新型β-内酰胺酶CTX-M-64首先在宋内志贺菌菌株UIH-1中鉴定，该菌株对头孢噻肟（MIC，1，024 μ g/ml）和头孢他啶（MIC，32 μ g/ml）表现出抗性。CTX-M-64的氨基酸序列显示CTX-M-15样β-内酰胺酶（N-和C-末端部分）和CTX-M-14样β-内酰胺酶（中心部分，氨基酸63至226）的嵌合结构，表明其来源于相应基因之间的同源重组。引入携带bla（CTX-M-64）的重组质粒赋予大肠杆菌对头孢噻肟的抗性，并且头孢噻肟和头孢他啶的活性在克拉维酸的存在下恢复。值得注意的是，CTX-M-64的产生也可以赋予头孢他啶一致的耐药性，这与大多数CTX-M型酶不同，后者对头孢他啶的水解很差。这些结果与用纯化的CTX-M-64酶测定的动力学参数一致。bla（CTX-M-64）基因上游侧接ISEcp 1序列，下游侧接orf 477序列。ISEcp 1和blaC（TX-M-64）的右反向重复序列（IRR）之间的45 bp间隔区的序列与ISEcp 1-bla（CTX-M-15-like）的完全相同。此外，在截短orf 477的右端存在ISEcp 1的假定IRR指示bla（CTX-M-64）基因中的ISEcp 1介导的转座事件。CTX-M-64通过可能的同源重组出现，表明CTX-M型β-内酰胺酶多样化的替代机制的天然潜力。
The plasmid-mediated novel beta-lactamase CTX-M-64 was first identified in Shigella sonnei strain UIH-1, which exhibited resistance to cefotaxime (MIC, 1,024 mu g/ml) and ceftazidime (MIC, 32 mu g/ml). The amino acid sequence of CTX-M-64 showed a chimeric structure of a CTX-M-15-like beta-lactamase (N- and C-terminal moieties) and a CTX-M-14-like beta-lactamase (central portion, amino acids 63 to 226), suggesting that it originated by homologous recombination between the corresponding genes. The introduction of a recombinant plasmid carrying bla(CTX-M-64) conferred resistance to cefotaxime in Escherichia coli, and the activities of cefotaxime and ceftazidime were restored in the presence of clavulanic acid. Of note, CTX-M-64 production could also confer consistent resistance to ceftazidime, which differs from the majority of CTX-M-type enzymes, which poorly hydrolyze ceftazidime. These results were consistent with the kinetic parameters determined with the purified CTX-M-64 enzyme. The bla(CTX-M-64) gene was flanked upstream by an ISEcp1 sequence and downstream by an orf477 sequence. The sequence of the 45-bp spacer region between the right inverted repeat (IRR) of ISEcp1 and blaC(TX-M-64) was exactly identical to that of ISEcp1-bla(CTX-M-15-like). Moreover, the presence of a putative IRR of ISEcp1 at the right end of truncated orf477 is indicative of an ISEcp1-mediated transposition event in the bla(CTX-M-64) gene. The emergence of CTX-M-64 by probable homologous recombination would suggest the natural potential of an alternative mechanism for the diversification of CTX-M-type beta-lactamases.