Molecular Epidemiology and Phylogenetic Distribution of the Escherichia coli pks Genomic Island

Molecular Epidemiology and Phylogenetic Distribution of the Escherichia coli pks Genomic Island
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DOI:
10.1128/jcm.00949-08
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发表时间:
2008-12-01
影响因子:
9.4
通讯作者:
Oswald, Eric
Oswald, Eric
中科院分区:
医学2区
文献类型:
--
作者:
Johnson, James R.;Johnston, Brian;Oswald, Eric

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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的关联,它编码的基因毒素大肠杆菌素,是不完全确定的。clbB和clbN(分别作为pks岛5'和3'区的标记)、clbA和clbQ(作为pks岛的补充标记)以及12个其它推测的ExPEC毒力基因。大肠杆菌分离株从住院退伍军人(62血液分离株和69粪便分离株)。血液和粪便分离株和clbB阳性和阴性分离株进行了比较,为66个新的和以前评估的性状。在14个新发现的性状中,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鉴定了系统发育组B2内具有极高毒力评分和高比例血液分离株的子集。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组和多个B2相关性状密切相关;通过主坐标分析,clbB和clbN比血液与粪便来源更好地划分数据集。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,它鉴定了特别高毒力的子集。这扩展了以前关于pks岛的工作,并支持大肠杆菌素系统作为潜在治疗靶点的研究。
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.