Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of extraintestinal pathogenic Escherichia coli
Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of extraintestinal pathogenic Escherichia coli
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DOI：
10.1111/j.1365-2958.2005.04985.x
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Sokurenko, EV
中科院分区：
文献类型：
--
作者：
Weissman, SJ;Chattopadhyay, S;Sokurenko, EV
大肠杆菌的 1 型菌毛介导与宿主上皮表面的甘露糖特异性粘附，由主要的抗原可变菌毛蛋白亚基 FimA 和位于菌毛尖端的较小的结构保守的粘附亚基 FimH 组成。我们分析了阴道和其他来源菌株中 fimA 和 fimH 的变异性，这些菌株属于肠外致病性大肠杆菌最突出的克隆群之一，由基于 O1:K1-、O2:K1- 和 O18:K1 的血清型组成。该组的多基因座序列分型 (MLST) 显示，这些菌株在基因组周围具有相同的（除了一个核苷酸位置外）八个管家基因座，并且属于公开可用的大肠杆菌 MLST 数据库定义的 ST95 复合体。多个高度多样化的 fimA 等位基因已通过水平转移引入 ST95 克隆复合体，其频率与定义主要 O 和 H 抗原的基因相当。然而，转移后并没有通过点突变发生进一步显着的 FimA 多样化。相比之下，虽然 fimH 等位基因也水平移动（与 fimA 位点一起），但它们以比管家基因或 fimA 更高的速率获得点氨基酸替换。这些 FimH 突变增强了与单甘露糖受体的结合以及人阴道上皮的细菌向性。在双半乳糖特异性 P 菌毛的 papG 和 papA 等位基因中，也分别观察到粘附亚基而非菌毛蛋白亚基的克隆内快速结构进化的类似模式。因此，虽然大肠杆菌菌毛的结构多样的菌毛蛋白亚基受到选择性压力，导致克隆之间频繁水平转移，但肠外大肠杆菌的粘附亚基却受到功能适应性氨基酸替代的强正选择（对于 fimH 和 papG，Dn/Ds > 1）。
Type 1 fimbriae of Escherichia coli mediate mannose-specific adhesion to host epithelial surfaces and consist of a major, antigenically variable pilin subunit, FimA, and a minor, structurally conserved adhesive subunit, FimH, located on the fimbrial tip. We have analysed the variability of fimA and fimH in strains of vaginal and other origin that belong to one of the most prominent clonal groups of extraintestinal pathogenic E. coli, comprised of O1:K1-, O2:K1- and O18:K1-based serotypes. Multiple locus sequence typing (MLST) of this group revealed that the strains have identical (at all but one nucleotide position) eight housekeeping loci around the genome and belong to the ST95 complex defined by the publicly available E. coli MLST database. Multiple highly diverse fimA alleles have been introduced into the ST95 clonal complex via horizontal transfer, at a frequency comparable to that of genes defining the major O- and H-antigens. However, no further significant FimA diversification has occurred via point mutation after the transfers. In contrast, while fimH alleles also move horizontally (along with the fimA loci), they acquire point amino acid replacements at a higher rate than either housekeeping genes or fimA. These FimH mutations enhance binding to monomannose receptors and bacterial tropism for human vaginal epithelium. A similar pattern of rapid within-clonal structural evolution of the adhesive, but not pilin, subunit is also seen, respectively, in papG and papA alleles of the di-galactose-specific P-fimbriae. Thus, while structurally diverse pilin subunits of E. coli fimbriae are under selective pressure for frequent horizontal transfer between clones, the adhesive subunits of extraintestinal E. coli are under strong positive selection (Dn/Ds > 1 for fimH and papG) for functionally adaptive amino acid replacements.