Model for evaluation of pathogenicity of extra-intestinal pathogenic Escherichia coli

本研究共收集501株大肠埃希菌，采用多位点序列分型方法(MLST)对其进行分析。结果表明，85.9%的肠外致病性大肠埃希菌(ExPEC)属于B2群，而在共生E.call分离株中，A/B1群占一半以上，40.2%的菌株属于B2群。根据MLST分析结果，B2群可分为8个亚群。而B2亚群分离株在尿液生长量、引入IL6的能力和体外对上皮细胞的黏附能力等方面没有明显差异，这可能是ExPEC的毒力特征。最近有报道称CDIA基因具有接触性杀菌活性，CDIA可能在与人体肠道其他细菌的竞争中发挥作用。急性膀胱炎呼肠埃希菌中有57.8%编码CDIA同源基因，CDIA广泛分布于B_2组各亚群以及A/B_1和D组。已知CDIA基因与编码PapGIII和hlyA的致病岛(PAI)相关。我们可以显示这些编码PapGIII、hlyA和CDA的PaI之间的遗传差异。为了研究哪种类型的大肠杆菌在人类肠道中的系统发育占主导地位，我们从健康志愿者的粪便中收集了共生大肠杆菌。在对共生大肠埃希菌进行基因分型和系统发育分析时发现，从一些健康志愿者中分离到一株B2-8菌株作为优势菌株已超过半年，表明该菌株具有适应环境的潜力。由于该菌株不具有CDIA，这一事实表明，另一种机制可能为该菌株提供了在人体肠道中占据优势地位的能力。我们需要进行进一步的分析，以研究在人体肠道中竞争性生长抑制的机制。

Total 501 Escherichia coli isolates were collected in this study, and were analyzed by using multi locus sequence typing method (MLST). As a result, 85.9% of extraintestinal pathogenetic E. coli (ExPEC) belonged to group B2, while among commensal E. call isolates, more than half were group A/B1, and 40.2% of the isolates belonged to group B2.Based on the results of MLST analysis, group B2 isolated divided into eight sub-groups. However the isolates from the B2 subgroup did not show any significant differences on growth capacity in urine, introducing ability of IL6, and adhesive potential to epithelial cells in vitro, which are suggested as virulence characters for ExPEC.Recently it is reported that cdiA gene has a contact bactericidal activity, and the cdiA might play a role for competition with other bacteria in human intestine. Among E. call isolates from acute cystitis, 57.8% of the isolates encoded the cdiA homologue, and the cdiA widely distributed in all subgroups of group B2 as well as A/B1 and D groups. The cdiA gene was known to be associated with pathogenicity islands (PAIs) encoding papGIII and hlyA. We could show genetic variation between these PAIs, which encoded papGIII, hlyA and cdiA.To investigate which type of E. coli on phylogeny is dominant in human intestine, we collected commensal E. coil form stool of healthy volunteers. During analysis of commensal E coli on genotype and phylogeny, we found out that a certain B2-8 strain was isolated from some healthy volunteers for more than half-year as the dominant strains, indicating that this strain has a potential to adjust for the environment. As this strain did not have the cdiA, this fact implied that another mechanism might provide ability to the strains as a dominant residence in the human intestine. We need to perform further analysis for investigating mechanisms on competitive growth inhibition in the human intestine.