Gilmour Matthew W, Thomson Nicholas R, Sanders Mandy, Parkhill Julian, Taylor Diane E
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alta., Canada T6G 2R3.
Plasmid. 2004 Nov;52(3):182-202. doi: 10.1016/j.plasmid.2004.06.006.
Horizontal transfer of resistance determinants amongst bacteria can be achieved by conjugative plasmid DNA elements. We have determined the complete 274,762 bp sequence of the incompatibility group H (IncH) plasmid R478, originally isolated from the Gram negative opportunistic pathogen Serratia marcescens. This self-transferable extrachromosomal genetic element contains 295 predicted genes, of which 144 are highly similar to coding sequences of IncH plasmids R27 and pHCM1. The regions of similarity among these three IncH plasmids principally encode core plasmid determinants (i.e., replication, partitioning and stability, and conjugative transfer) and we conducted a comparative analysis to define the minimal IncHI plasmid backbone determinants. No resistance determinants are included in the backbone and most of the sequences unique to R478 were contained in a large contiguous region between the two transfer regions. These findings indicate that plasmid evolution occurs through gene acquisition/loss predominantly in regions outside of the core determinants. Furthermore, a modular evolution for R478 was signified by the presence of gene neighbors or operons that were highly related to sequences from a wide range of chromosomal, transposon, and plasmid elements. The conjugative transfer regions are most similar to sequences encoded on SXT, Rts1, pCAR1, R391, and pRS241d. The dual partitioning modules encoded on R478 resemble numerous sequences; including pMT1, pCTX-M3, pCP301, P1, P7, and pB171. R478 also codes for resistance to tetracycline (Tn10), chloramphenicol (cat), kanamycin (aphA), mercury (similar to Tn21), silver (similar to pMG101), copper (similar to pRJ1004), arsenic (similar to pYV), and tellurite (two separate regions similar to IncHI2 ter determinants and IncP kla determinants). Other R478-encoded sequences are related to Tn7, IS26, tus, mucAB, and hok, where the latter is surrounded by insLKJ, and could potentially be involved in post-segregation killing. The similarity to a diverse set of bacterial sequences highlights the ability of horizontally transferable DNA elements to acquire and disseminate genetic traits through the bacterial gene pool.
细菌间耐药决定因子的水平转移可通过接合性质粒DNA元件来实现。我们已测定了不相容群H（IncH）质粒R478完整的274,762 bp序列，该质粒最初从革兰氏阴性机会致病菌粘质沙雷氏菌中分离得到。这个可自我转移的染色体外遗传元件包含295个预测基因，其中144个与IncH质粒R27和pHCM1的编码序列高度相似。这三种IncH质粒之间的相似区域主要编码核心质粒决定因子（即复制、分配与稳定性以及接合转移），并且我们进行了比较分析以确定最小的IncHI质粒骨干决定因子。骨干中不包含耐药决定因子，R478特有的大多数序列位于两个转移区域之间的一个大的连续区域内。这些发现表明质粒进化主要通过核心决定因子区域之外的基因获得/丢失来发生。此外，R478的模块化进化表现为存在与来自广泛的染色体、转座子和质粒元件的序列高度相关的基因邻域或操纵子。接合转移区域与SXT、Rts1、pCAR1、R391和pRS241d上编码的序列最为相似。R478上编码的双分配模块类似于许多序列；包括pMT1、pCTX-M3、pCP301、P1、P7和pB171。R478还编码对四环素（Tn10）、氯霉素（cat）、卡那霉素（aphA）、汞（类似于Tn21）、银（类似于pMG101）、铜（类似于pRJ1004）、砷（类似于pYV）和亚碲酸盐（两个分别类似于IncHI2 ter决定因子和IncP kla决定因子的区域）的抗性。其他R478编码的序列与Tn7、IS26、tus、mucAB和hok相关，其中后者被insLKJ包围，并且可能参与后分离杀伤。与多种细菌序列的相似性突出了水平可转移DNA元件通过细菌基因库获取和传播遗传性状的能力。
