Johnson James R, Johnston Brian, Kuskowski Michael A, Nougayrede Jean-Philippe, Oswald Eric
Medical Service, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.
J Clin Microbiol. 2008 Dec;46(12):3906-11. doi: 10.1128/JCM.00949-08. Epub 2008 Oct 22.
Epidemiological and phylogenetic associations of the pks genomic island of extraintestinal pathogenic Escherichia coli (ExPEC), which encodes the genotoxin colibactin, are incompletely defined. clbB and clbN (as markers for the 5' and 3' regions of the pks island, respectively), clbA and clbQ (as supplemental pks island markers), and 12 other putative ExPEC virulence genes were newly sought by PCR among 131 published E. coli isolates from hospitalized veterans (62 blood isolates and 69 fecal isolates). Blood and fecal isolates and clbB-positive and -negative isolates were compared for 66 newly and previously assessed traits. Among the 14 newly sought traits, clbB and clbN (colibactin polyketide synthesis system), hra (heat-resistant agglutinin), and vat (vacuolating toxin) were significantly associated with bacteremia. clbB and clbN identified a subset within phylogenetic group B2 with extremely high virulence scores and a high proportion of blood isolates. However, by multivariable analysis, other traits were more predictive of blood source than clbB and clbN were; indeed, among the newly sought traits, only pic significantly predicted bacteremia (negative association). By correspondence analysis, clbB and clbN were closely associated with group B2 and multiple B2-associated traits; by principal coordinate analysis, clbB and clbN partitioned the data set better than did blood versus fecal source. Thus, the pks island was significantly associated with bacteremia, multiple ExPEC-associated virulence genes, and group B2, and within group B2, it identified an especially high-virulence subset. This extends previous work regarding the pks island and supports investigation of the colibactin system as a potential therapeutic target.
编码基因毒素大肠杆菌素的肠外致病性大肠杆菌（ExPEC）的pks基因组岛的流行病学和系统发育关联尚未完全明确。通过PCR在131株已发表的来自住院退伍军人的大肠杆菌分离株（62株血液分离株和69株粪便分离株）中重新寻找clbB和clbN（分别作为pks岛5'和3'区域的标记）、clbA和clbQ（作为补充的pks岛标记）以及其他12个假定的ExPEC毒力基因。对血液和粪便分离株以及clbB阳性和阴性分离株进行了66个新评估和先前评估的性状比较。在14个新寻找的性状中，clbB和clbN（大肠杆菌素聚酮合成系统）、hra（耐热凝集素）和vat（空泡毒素）与菌血症显著相关。clbB和clbN在系统发育B2组中鉴定出一个毒力得分极高且血液分离株比例很高的亚组。然而，通过多变量分析，其他性状比clbB和clbN更能预测血液来源；事实上，在新寻找的性状中，只有pic显著预测菌血症（负相关）。通过对应分析，clbB和clbN与B2组以及多个与B2相关的性状密切相关；通过主坐标分析，clbB和clbN对数据集的划分比血液与粪便来源更好。因此，pks岛与菌血症、多个ExPEC相关毒力基因和B2组显著相关，并且在B2组内，它鉴定出一个特别高毒力的亚组。这扩展了先前关于pks岛的研究工作，并支持将大肠杆菌素系统作为潜在治疗靶点进行研究。
