Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil.
BMC Genomics. 2014 Jan 22;15:54. doi: 10.1186/1471-2164-15-54.
Klebsiella pneumoniae is an important opportunistic pathogen associated with nosocomial and community-acquired infections. A wide repertoire of virulence and antimicrobial resistance genes is present in K. pneumoniae genomes, which can constitute extra challenges in the treatment of infections caused by some strains. K. pneumoniae Kp13 is a multidrug-resistant strain responsible for causing a large nosocomial outbreak in a teaching hospital located in Southern Brazil. Kp13 produces K. pneumoniae carbapenemase (KPC-2) but is unrelated to isolates belonging to ST 258 and ST 11, the main clusters associated with the worldwide dissemination of KPC-producing K. pneumoniae. In this report, we perform a genomic comparison between Kp13 and each of the following three K. pneumoniae genomes: MGH 78578, NTUH-K2044 and 342.
We have completely determined the genome of K. pneumoniae Kp13, which comprises one chromosome (5.3 Mbp) and six plasmids (0.43 Mbp). Several virulence and resistance determinants were identified in strain Kp13. Specifically, we detected genes coding for six beta-lactamases (SHV-12, OXA-9, TEM-1, CTX-M-2, SHV-110 and KPC-2), eight adhesin-related gene clusters, including regions coding for types 1 (fim) and 3 (mrk) fimbrial adhesins. The rmtG plasmidial 16S rRNA methyltransferase gene was also detected, as well as efflux pumps belonging to five different families. Mutations upstream the OmpK35 porin-encoding gene were evidenced, possibly affecting its expression. SNPs analysis relative to the compared strains revealed 141 mutations falling within CDSs related to drug resistance which could also influence the Kp13 lifestyle. Finally, the genetic apparatus for synthesis of the yersiniabactin siderophore was identified within a plasticity region. Chromosomal architectural analysis allowed for the detection of 13 regions of difference in Kp13 relative to the compared strains.
Our results indicate that the plasticity occurring at many hierarchical levels (from whole genomic segments to individual nucleotide bases) may play a role on the lifestyle of K. pneumoniae Kp13 and underlie the importance of whole-genome sequencing to study bacterial pathogens. The general chromosomal structure was somewhat conserved among the compared bacteria, and recombination events with consequent gain/loss of genomic segments appears to be driving the evolution of these strains.
肺炎克雷伯菌是一种重要的机会致病菌，与医院获得性和社区获得性感染有关。肺炎克雷伯菌基因组中存在广泛的毒力和抗菌药物耐药基因，这可能给一些菌株引起的感染治疗带来额外的挑战。肺炎克雷伯菌 Kp13 是一种多药耐药株，导致巴西南部一所教学医院发生大规模医院感染暴发。Kp13 产生肺炎克雷伯菌碳青霉烯酶（KPC-2），但与 ST258 和 ST11 无关，ST258 和 ST11 是与全球传播产 KPC 肺炎克雷伯菌有关的主要聚类。在本报告中，我们对 Kp13 与以下三种肺炎克雷伯菌基因组中的每一种进行了基因组比较：MGH 78578、NTUH-K2044 和 342。
我们已经完全确定了肺炎克雷伯菌 Kp13 的基因组，它由一个染色体（5.3 Mbp）和六个质粒（0.43 Mbp）组成。在 Kp13 中发现了几种毒力和耐药决定因素。具体来说，我们检测到编码六种β-内酰胺酶（SHV-12、OXA-9、TEM-1、CTX-M-2、SHV-110 和 KPC-2）的基因、八个黏附相关基因簇，包括编码 1 型（fim）和 3 型（mrk）菌毛黏附素的区域。还检测到 rmtG 质粒 16S rRNA 甲基转移酶基因以及属于五个不同家族的外排泵。证据表明，OmpK35 孔蛋白编码基因上游的突变可能影响其表达。与比较菌株相关的 SNPs 分析显示，在与耐药相关的 CDS 中发现了 141 个突变，这可能会影响 Kp13 的生活方式。最后，在一个可塑区域内鉴定出了耶尔森氏菌铁载体合成的遗传装置。染色体结构分析检测到 Kp13 与比较菌株相比有 13 个差异区域。
我们的结果表明，许多层次（从整个基因组片段到单个核苷酸碱基）发生的可塑性可能在肺炎克雷伯菌 Kp13 的生活方式中发挥作用，并强调了全基因组测序在研究细菌病原体中的重要性。比较细菌的一般染色体结构有些保守，重组事件导致基因组片段的获得/丢失似乎正在推动这些菌株的进化。
