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Title: Allelic variation contributes to bacterial host specificity

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. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [4];  [5];  [5];  [6];  [7];  [8];  [8]; ORCiD logo [9];  [10];  [10];  [1] more »;  [1] « less
  1. Univ. of Pennsylvania School of Veterinary Medicine, Philadelphia, PA (United States)
  2. San Diego State Univ., San Diego, CA (United States)
  3. South Dakota State Univ., Brookings, SD (United States)
  4. Pennsylvania Department of Health, Exton, PA (United States)
  5. US FDA Office of Research, Laurel, MD (United States). Center for Veterinary Medicine
  6. Pasteur Institute, Paris (France)
  7. Univ. of Liege, (Belgium)
  8. Univ. of Maryland School of Medicine, Baltimore, MD (United States). Institute for Genome Sciences
  9. San Diego State Univ., San Diego, CA (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
  10. Univ. of Pennsylvania, Philadelphia, PA (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1258603
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Yue, Min, Han, Xiangan, Masi, Leon De, Zhu, Chunhong, Ma, Xun, Zhang, Junjie, Wu, Renwei, Schmieder, Robert, Kaushik, Radhey S., Fraser, George P., Zhao, Shaohua, McDermott, Patrick F., Weill, François-Xavier, Mainil, Jacques G., Arze, Cesar, Fricke, W. Florian, Edwards, Robert A., Brisson, Dustin, Zhang, Nancy R., Rankin, Shelley C., and Schifferli, Dieter M. Allelic variation contributes to bacterial host specificity. United States: N. p., 2015. Web. doi:10.1038/ncomms9754.
Yue, Min, Han, Xiangan, Masi, Leon De, Zhu, Chunhong, Ma, Xun, Zhang, Junjie, Wu, Renwei, Schmieder, Robert, Kaushik, Radhey S., Fraser, George P., Zhao, Shaohua, McDermott, Patrick F., Weill, François-Xavier, Mainil, Jacques G., Arze, Cesar, Fricke, W. Florian, Edwards, Robert A., Brisson, Dustin, Zhang, Nancy R., Rankin, Shelley C., & Schifferli, Dieter M. Allelic variation contributes to bacterial host specificity. United States. doi:10.1038/ncomms9754.
Yue, Min, Han, Xiangan, Masi, Leon De, Zhu, Chunhong, Ma, Xun, Zhang, Junjie, Wu, Renwei, Schmieder, Robert, Kaushik, Radhey S., Fraser, George P., Zhao, Shaohua, McDermott, Patrick F., Weill, François-Xavier, Mainil, Jacques G., Arze, Cesar, Fricke, W. Florian, Edwards, Robert A., Brisson, Dustin, Zhang, Nancy R., Rankin, Shelley C., and Schifferli, Dieter M. Fri . "Allelic variation contributes to bacterial host specificity". United States. doi:10.1038/ncomms9754. https://www.osti.gov/servlets/purl/1258603.
@article{osti_1258603,
title = {Allelic variation contributes to bacterial host specificity},
author = {Yue, Min and Han, Xiangan and Masi, Leon De and Zhu, Chunhong and Ma, Xun and Zhang, Junjie and Wu, Renwei and Schmieder, Robert and Kaushik, Radhey S. and Fraser, George P. and Zhao, Shaohua and McDermott, Patrick F. and Weill, François-Xavier and Mainil, Jacques G. and Arze, Cesar and Fricke, W. Florian and Edwards, Robert A. and Brisson, Dustin and Zhang, Nancy R. and Rankin, Shelley C. and Schifferli, Dieter M.},
abstractNote = {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. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.},
doi = {10.1038/ncomms9754},
journal = {Nature Communications},
number = ,
volume = 6,
place = {United States},
year = {2015},
month = {10}
}

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