Sorsa Liisa Johanna, Feldmann Friederike, Hildinger Kirsten, Dufke Severin, Schubert Sören
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Marchioninistr. 17, D-81377 München, Germany.
Int J Med Microbiol. 2007 Apr;297(2):83-95. doi: 10.1016/j.ijmm.2006.11.007. Epub 2007 Feb 5.
Extraintestinal pathogenic Escherichia coli (ExPEC) are a major cause of urinary tract infections, sepsis, and neonatal meningitis. A variety of virulence factors in these strains is encoded by mobile genetic elements, such as transposons or pathogenicity islands (PAIs). Using subtractive cloning of ExPEC genomes, we recently detected short DNA fragments, which were significantly associated with the extraintestinal virulent phenotype. In this study, we identified four novel genomic DNA regions of the highly virulent uropathogenic E. coli strain JS299 carrying these previously identified DNA fragments. Characterization of the partial sequences of the genomic DNA regions revealed complex DNA arrangements with variable genetic compositions regarding the G+C contents and codon usage patterns. The prevalence of 15 previously uncharacterized genes was determined in a collection of clinical ExPECs and commensal E. coli strains by means of DNA microarray analyses. From this, 13 novel DNA sequences were demonstrated to be significantly associated with extraintestinal virulent strains, and thus may represent new virulence traits. Beside genes predicted to play a role in metabolic functions, such as sucrose utilization (scr), we identified DNA sequences shared by both ExPEC and enteropathogenic E. coli (EPEC). These sequences were significantly more prevalent among ExPECs when compared to commensal E. coli isolates. Our results support the idea of a considerable genetic variability among ExPEC strains and suggest that the novel genomic determinants described in this study may contribute to the ExPEC virulence.
肠外致病性大肠杆菌（ExPEC）是尿路感染、败血症和新生儿脑膜炎的主要病因。这些菌株中的多种毒力因子由可移动遗传元件编码，如转座子或致病岛（PAI）。通过对ExPEC基因组进行消减克隆，我们最近检测到一些短DNA片段，它们与肠外致病表型显著相关。在本研究中，我们鉴定了携带这些先前鉴定的DNA片段的高毒力尿路致病性大肠杆菌菌株JS299的四个新的基因组DNA区域。对这些基因组DNA区域部分序列的表征揭示了复杂的DNA排列，其G+C含量和密码子使用模式的遗传组成各不相同。通过DNA微阵列分析，在一组临床ExPEC和共生大肠杆菌菌株中测定了15个先前未鉴定基因的流行情况。由此发现，13个新的DNA序列与肠外致病菌株显著相关，因此可能代表新的毒力特征。除了预测在代谢功能中起作用的基因，如蔗糖利用（scr）基因外，我们还鉴定了ExPEC和肠致病性大肠杆菌（EPEC）共有的DNA序列。与共生大肠杆菌分离株相比，这些序列在ExPEC中更为普遍。我们的结果支持ExPEC菌株存在相当大的遗传变异性这一观点，并表明本研究中描述的新基因组决定因素可能有助于ExPEC的毒力。
