Department of Molecular Biology, Section of Microbiology, University of Siena, Siena, Italy.
Antimicrob Agents Chemother. 2011 Jun;55(6):2735-42. doi: 10.1128/AAC.01736-10. Epub 2011 Mar 14.
Proteus mirabilis isolates obtained in 1999 to 2008 from three European countries were analyzed; all carried chromosomal AmpC-type cephalosporinase bla(CMY) genes from a Citrobacter freundii origin (bla(CMY-2)-like genes). Isolates from Poland harbored several bla(CMY) genes (bla(CMY-4), bla(CMY-12), bla(CMY-14), bla(CMY-15), and bla(CMY-38) and the new gene bla(CMY-45)), while isolates from Italy and Greece harbored bla(CMY-16) only. Earlier isolates with bla(CMY-4) or bla(CMY-12), recovered in France from Greek and Algerian patients, were also studied. All isolates showed striking similarities. Their bla(CMY) genes resided within ISEcp1 transposition modules, named Tn6093, characterized by a 110-bp distance between ISEcp1 and bla(CMY), and identical fragments of both C. freundii DNA and a ColE1-type plasmid backbone. Moreover, these modules were inserted into the same chromosomal site, within the pepQ gene. Since ColE1 plasmids carrying ISEcp1 with similar C. freundii DNA fragments (Tn6114) had been identified earlier, it is likely that a similar molecule had mediated at some stage this DNA transfer between C. freundii and P. mirabilis. In addition, isolates with bla(CMY-12), bla(CMY-15), and bla(CMY-38) genes harbored a second bla(CMY) copy within a shorter ISEcp1 module (Tn6113), always inserted downstream of the ppiD gene. Sequence analysis of all mobile bla(CMY-2)-like genes indicated that those integrated in the P. mirabilis chromosome form a distinct cluster that may have evolved by the stepwise accumulation of mutations. All of these observations, coupled to strain typing data, suggest that the bla(CMY) genes studied here may have originated from a single ISEcp1-mediated mobilization-transfer-integration process, followed by the spread and evolution of a P. mirabilis clone over time and a large geographic area.
对 1999 年至 2008 年间从三个欧洲国家分离得到的奇异变形杆菌进行分析；所有菌株均携带源自柠檬酸杆菌的染色体型头孢菌素酶 bla(CMY)基因（bla(CMY-2)-样基因）。波兰分离株携带多个 bla(CMY)基因（bla(CMY-4)、bla(CMY-12)、bla(CMY-14)、bla(CMY-15)和 bla(CMY-38)以及新基因 bla(CMY-45)），而意大利和希腊分离株仅携带 bla(CMY-16)。此前在法国从希腊和阿尔及利亚患者中分离到的携带 bla(CMY-4)或 bla(CMY-12)的早期分离株也进行了研究。所有分离株均显示出显著的相似性。它们的 bla(CMY)基因位于 ISEcp1 转座模块内，命名为 Tn6093，其特征是 ISEcp1 与 bla(CMY)之间有 110bp 的距离，且 C. freundii DNA 和 ColE1 型质粒骨架的片段完全相同。此外，这些模块插入到 pepQ 基因内的相同染色体位置。由于此前已鉴定出携带具有相似 C. freundii DNA 片段的 ISEcp1 的 ColE1 质粒（Tn6114），因此很可能在某个阶段，该 DNA 转移是由奇异变形杆菌和 C. freundii 之间的类似分子介导的。此外，携带 bla(CMY-12)、bla(CMY-15)和 bla(CMY-38)基因的分离株在较短的 ISEcp1 模块（Tn6113）内携带第二个 bla(CMY)拷贝，该模块始终插入 ppiD 基因的下游。对所有移动 bla(CMY-2)-样基因的序列分析表明，整合到奇异变形杆菌染色体中的基因形成一个独特的簇，可能是通过突变的逐步积累而进化的。所有这些观察结果，加上菌株分型数据，表明此处研究的 bla(CMY)基因可能起源于单个由 ISEcp1 介导的动员-转移-整合过程，随后是一个奇异变形杆菌克隆在时间和大地理区域内的传播和进化。
