Abstract
Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.
Highlights
Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease
NsSNPs in the core genomes associated with specific hosts, as shown in a heat map of nonsynonymous single-nucleotide polymorphisms (nsSNPs) (Supplementary Fig. 1b), suggesting that host preferences of individual Typhimurium strains involves unique combinations of cell surface and exported allelic proteins
Typhimurium’s association to diverse hosts was its allelic variants of surface or exported proteins, we further investigated the potential role of a representative set of these proteins in host– pathogen interactions that may contribute to host adaptation
Summary
Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Typhimurium cause a typhoid-like disease in susceptible mice, particular phage types such as DT2 or DT99 can cause systemic infections in pigeons[11] and the multi-locus sequence type ST313 causes systemic infection in humans and chickens[12,13] It appears that both inter- and intra-serovar variation have a role in host range and disease severity. Functional analysis of identified variants of the FimH adhesin confirmed their biological relevance in modulating host-specific binding that can contribute to host-adaptation and to the Salmonella strain pathotype
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