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

Abstract

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.

Escherichia coli Common Pilus (ECP) Targets Arabinosyl Residues in Plant Cell Walls to Mediate Adhesion to Fresh Produce Plants

“…However, differences in the EcpD mature protein may be sufficient to alter receptor specificity as has been observed for type 1 fimbriae (65). ECP tropism for pectic arabinan was confirmed with pectate lyase treatment, which degrades homogalacturonan chains, the main component of pectin polysaccharides (66), and releases the arabinose-substituted pectin polysaccharides.…”

Host Specificity of Bacterial Pathogens

“…Genomic decay of genes encoding these intestinal colonization factors is evident in host-restricted Salmonella serovars, as pseudogenes are present in 7 of 11 fimbrial operons in S. Typhi strain CT18 (Townsend et al 2001), 8 of 12 fimbrial operons in S. Gallinarium (Thomson et al 2008), and 3 of 12 fimbrial operons in S. Paratyphi A . It has been postulated that mutations that alter adhesion-binding specificity or affinity can also contribute to adaptation to different host environments (Kisiela et al 2012). The generalist S. Typhimurium uses tetrathionate respiration encoded by the ttrRS/ttrBCA gene cluster to out-compete microbes in the gut during its fecal -oral transmission cycle (Winter et al 2010a).…”

An Environmental Shiga Toxin-Producing Escherichia coli O145 Clonal Population Exhibits High-Level Phenotypic Variation That Includes Virulence Traits

“…Such beneficial mutations have been described for diverse bacteria, including E. coli, for improved nutrient scavenging, increased resistance to stresses or antibiotics (15)(16)(17)(18), and enhanced pathogenicity in bacterial pathogens, a phenomenon also known as patho-adaptation (19,20). Classical examples of patho-adaptation include the genes encoding lysine decarboxylase (20)(21)(22)(23)(24), type I fimbrial adhesin (25)(26)(27)(28)(29), and the curli fimbriae (29). Loss-of-function mutations in genes encoding the global transcriptional regulators RpoS and RcsB were reported for the STEC population, generating variants with distinct physiological properties, such as the expression of virulence genes, biofilm formation, stress resistances, and catabolic potential (30,31).…”