Evolution of Salmonella enterica Virulence via Point Mutations in the Fimbrial Adhesin

PLoS Pathogens

Roderick I. Mackie¹  Emily W. Lankau¹  Maciej Ugorski²  Krzysztof Grzymajlo²  Steven Clegg³  Sujay Chattopadhyay⁴  Stephen J. Libby⁴  Veronika Tchesnokova⁴  Ferric C. Fang⁴  Evgeni V. Sokurenko⁴  Dagmara I. Kisiela⁴  Joyce E. Karlinsey⁴  Jeremy J. Kramer⁴  Mansour Samadpour⁵  Viktoriya Beskhlebnaya⁵ 

[1] Department of Animal Sciences, University of Illinois, Urbana, Illinois, United States of America;Department of Biochemistry, Pharmacology and Toxicology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland;Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America;Department of Microbiology, University of Washington, Seattle, Washington, United States of America;Institute for Environmental Health, Lake Forest Park, Washington, United States of America

关键词: Salmonella;    Salmonella enterica;    Salmonella typhimurium;    Pili;    fimbriae;    Point mutation;    Salmonella typhi;    Adhesins;    Mannose;   

DOI  :  10.1371/journal.ppat.1002733

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY