Yue, MinHan, XianganDe Masi, LeonZhu, ChunhongMa, XunZhang, JunjieWu, RenweiSchmieder, RobertKaushik, Radhey SFraser, George PZhao, ShaohuaMcDermott, Patrick FWeill, François-XavierMainil, Jacques GArze, CesarFricke, W. FlorianEdwards, Robert ABrisson, DustinZhang, Nancy RRankin, Shelley CSchifferli, Dieter M2023-05-232023-05-232015-10-302018-07-17https://repository.upenn.edu/handle/20.500.14332/48024Understanding 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.This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit (http://creativecommons.org/licenses/by/4.0/).Bacterial Infections and MycosesBacteriologyBusinessGenetics and GenomicsImmunology and Infectious DiseaseStatistics and ProbabilityReport