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Nat Commun. 2015 Oct 30;6:8754. doi: 10.1038/ncomms9754.

Allelic variation contributes to bacterial host specificity.

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Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce St, Philadelphia, Pennsylvania 19104, USA.
Department of Computer Science, College of Sciences, San Diego State University, 5500 Campanile Drive, PS 106, San Diego, California 92182, USA.
Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota 57007, USA.
Department of Biology and Microbiology, Box-2140D, South Dakota State University, Brookings, South Dakota 57007, USA.
Pennsylvania Department of Health, Bureau of Laboratories, 110 Pickering Way, Exton, Pennsylvania 19341, USA.
Division of Animal and Food Microbiology, Center for Veterinary Medicine, US FDA, Office of Research, 8401 Muirkirk Road, Laurel, Maryland 20708, USA.
Institut Pasteur, Unité des Bactéries Pathogènes Entériques, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Bacteriology, Department of Infectious Diseases, Faculty of Veterinary Medicine and Institute for Fundamental and Applied Research in Animal Health (FARAH), Campus du Sart Tilman, Bât. B43a, University of Liège, 4000 Liège, Belgium.
Institute for Genome Sciences, Department for Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, 801W Baltimore St, Maryland 21201, USA.
Mathematics and Computer Science Division, Argonne National Laboratory, 9700S. Cass Avenue, Argonne, Illinois 60439, USA.
Department of Biology, School of Art and Science, University of Pennsylvania, 209 Leidy Laboratories, 433S. University Avenue, Philadelphia, Pennsylvania 19104, USA.
Department of Statistics, Wharton School, University of Pennsylvania, 3730 Walnut Street, Philadelphia, Pennsylvania 19104, USA.


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.

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