Evolution of Salmonella enterica virulence via point mutations in the fimbrial adhesin.
Evolution of Salmonella enterica virulence via point mutations in the fimbrial adhesin.
复制标题
DOI：
10.1371/journal.ppat.1002733
复制
发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Sokurenko EV
中科院分区：
文献类型：
--
作者：
Kisiela DI;Chattopadhyay S;Libby SJ;Karlinsey JE;Fang FC;Tchesnokova V;Kramer JJ;Beskhlebnaya V;Samadpour M;Grzymajlo K;Ugorski M;Lankau EW;Mackie RI;Clegg S;Sokurenko EV
尽管大多数致病性沙门氏菌血清型能够感染许多不同的动物物种，通常产生自限性胃肠炎，但具有窄宿主特异性的血清型表现出增加的毒力，并且它们的感染经常导致致命的全身性疾病。在我们的研究中，对来自肠道沙门氏菌各种血清型的甘露糖特异性1型菌毛粘附素FimH进行的遗传和功能分析表明，FimH的特定突变变体在宿主适应性（全身侵入性）血清型中很常见。我们已经发现，虽然粘附素的低结合剪切依赖性表型在广泛的宿主范围（通常是全身非侵入性的）沙门氏菌中保留，但大多数宿主适应的血清型表达具有两种可选表型之一的FimH变体：与甘露糖的结合显著增加（如在沙门氏菌中）。伤寒沙门氏菌S.丙型副伤寒、沙门氏菌都柏林和S.霍乱弧菌），或完全丧失甘露糖结合活性（如在S。副伤寒B、S. Choleraesuis和S. Gallinarum）。FimH在宿主适应性沙门氏菌中的功能多样性来自最近获得的结构突变。许多突变具有趋同性，表明强阳性选择。FimH的高结合表型导致上皮细胞和巨噬细胞的细菌粘附和侵袭性增加，通常在获得非结合表型之前。总的来说，这些观察结果表明，激活或失活的甘露糖特异性的粘附特性在不同的系统侵入性血清型沙门氏菌反映了他们的动态轨迹适应特定的主机的生活方式。总之，我们的研究表明，点突变是积极选择的目标，除了水平基因转移和基因组降解事件，可以有助于沙门氏菌的差异病理适应性进化。沙门氏菌宿主适应的过程传统上被认为涉及获得编码特定毒力因子的新遗传元件或代表致病性更强菌株的基因的丢失。在这里，通过对甘露糖敏感的菌毛粘附素FimH的分析，我们证明了除了水平基因转移和基因组降解外，单个氨基酸替换在沙门氏菌的差异适应性进化中起着重要作用。我们表明，收购特定的结构突变FimH变体的主机适应（全身侵入性）血清型的结果显着增强或，替代地，完全灭活甘露糖结合，而全身非侵入性血清型保留原始的相对低结合（剪切依赖性）表型。系统发育分析表明，这些突变通常是一个收敛的性质，并在强阳性选择下发生，说明了点氨基酸变化在宿主适应沙门氏菌的收敛进化中的作用。虽然我们发现高结合突变体的细菌侵袭性和细胞侵袭性增加，但FimH中非结合突变的生理作用仍有待确定。
Whereas the majority of pathogenic Salmonella serovars are capable of infecting many different animal species, typically producing a self-limited gastroenteritis, serovars with narrow host-specificity exhibit increased virulence and their infections frequently result in fatal systemic diseases. In our study, a genetic and functional analysis of the mannose-specific type 1 fimbrial adhesin FimH from a variety of serovars of Salmonella enterica revealed that specific mutant variants of FimH are common in host-adapted (systemically invasive) serovars. We have found that while the low-binding shear-dependent phenotype of the adhesin is preserved in broad host-range (usually systemically non-invasive) Salmonella, the majority of host-adapted serovars express FimH variants with one of two alternative phenotypes: a significantly increased binding to mannose (as in S. Typhi, S. Paratyphi C, S. Dublin and some isolates of S. Choleraesuis), or complete loss of the mannose-binding activity (as in S. Paratyphi B, S. Choleraesuis and S. Gallinarum). The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations. Many of the mutations are of a convergent nature indicative of strong positive selection. The high-binding phenotype of FimH that leads to increased bacterial adhesiveness to and invasiveness of epithelial cells and macrophages usually precedes acquisition of the non-binding phenotype. Collectively these observations suggest that activation or inactivation of mannose-specific adhesive properties in different systemically invasive serovars of Salmonella reflects their dynamic trajectories of adaptation to a life style in specific hosts. In conclusion, our study demonstrates that point mutations are the target of positive selection and, in addition to horizontal gene transfer and genome degradation events, can contribute to the differential pathoadaptive evolution of Salmonella. The process of Salmonella host-adaptation is traditionally considered to involve acquisition of novel genetic elements encoding specific virulence factors or loss of genes representing liability for the more pathogenic strains. Here, by analysis of the mannose-sensitive fimbrial adhesin FimH, we demonstrate that in addition to horizontal gene transfer and genome degradation, single amino acid replacement plays an important role in the differential adaptive evolution of Salmonella. We show that acquisition of specific structural mutations in FimH variants of host-adapted (systemically invasive) serovars results in either significantly enhanced or, alternatively, completely inactivated mannose-binding, whereas systemically non-invasive serovars retain a primordial relatively low-binding (shear-dependent) phenotype. A phylogenetic analysis indicates that these mutations are commonly of a convergent nature and occur under strong positive selection illustrating the role of point amino acid changes in convergent evolution of host-adapted Salmonella. Although we show increased bacterial adhesiveness and cell-invasiveness of the high-binding mutants, the physiologic role of the non-binding mutations in FimH remains to be determined.
登录
查看更多内容
影响因子：
14.9
作者：
Chiu CH;Tang P;Chu C;Hu S;Bao Q;Yu J;Chou YY;Wang HS;Lee YS
通讯作者：
Lee YS
影响因子：
5.1
作者：
Briones, V;Téllez, S;Fernández-Garayzábal, JF
通讯作者：
Fernández-Garayzábal, JF
影响因子：
3.1
作者：
Althouse, C;Patterson, S;Isaacson, RE
通讯作者：
Isaacson, RE
影响因子：
3.2
作者：
Field, Terry R.;Layton, Abigail N.;Galyov, Edouard E.
通讯作者：
Galyov, Edouard E.
影响因子：
15.9
作者：
Groisman, EA;Ochman, H
通讯作者：
Ochman, H