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YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium.
Infect Immun. 2018 11; 86(11)II

Abstract

Mutations in σE-regulated lipoproteins have previously been shown to impact bacterial viability under conditions of stress and during in vivo infection. YraP is conserved across a number of Gram-negative pathogens, including Neisseria meningitidis, where the homolog is a component of the Bexsero meningococcal group B vaccine. Investigations using laboratory-adapted Escherichia coli K-12 have shown that yraP mutants have elevated sensitivity to a range of compounds, including detergents and normally ineffective antibiotics. In this study, we investigate the role of the outer membrane lipoprotein YraP in the pathogenesis of Salmonella enterica serovar Typhimurium. We show that mutations in S Typhimurium yraP result in a defective outer membrane barrier with elevated sensitivity to a range of compounds. This defect is associated with attenuated virulence in an oral infection model and during the early stages of systemic infection. We show that this attenuation is not a result of defects in lipopolysaccharide and O-antigen synthesis, changes in outer membrane protein levels, or the ability to adhere to and invade eukaryotic cell lines in vitro.

Authors+Show Affiliations

Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom i.r.henderson@bham.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30201701

Citation

Morris, Faye C., et al. "YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella Enterica Serovar Typhimurium." Infection and Immunity, vol. 86, no. 11, 2018.
Morris FC, Wells TJ, Bryant JA, et al. YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium. Infect Immun. 2018;86(11).
Morris, F. C., Wells, T. J., Bryant, J. A., Schager, A. E., Sevastsyanovich, Y. R., Squire, D. J. P., Marshall, J., Isom, G. L., Rooke, J., Maderbocus, R., Knowles, T. J., Overduin, M., Rossiter, A. E., Cunningham, A. F., & Henderson, I. R. (2018). YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium. Infection and Immunity, 86(11). https://doi.org/10.1128/IAI.00829-17
Morris FC, et al. YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella Enterica Serovar Typhimurium. Infect Immun. 2018;86(11) PubMed PMID: 30201701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium. AU - Morris,Faye C, AU - Wells,Timothy J, AU - Bryant,Jack A, AU - Schager,Anna E, AU - Sevastsyanovich,Yanina R, AU - Squire,Derrick J P, AU - Marshall,Jennifer, AU - Isom,Georgia L, AU - Rooke,Jessica, AU - Maderbocus,Riyaz, AU - Knowles,Timothy J, AU - Overduin,Michael, AU - Rossiter,Amanda E, AU - Cunningham,Adam F, AU - Henderson,Ian R, Y1 - 2018/10/25/ PY - 2017/11/16/received PY - 2018/07/30/accepted PY - 2018/9/12/pubmed PY - 2019/4/13/medline PY - 2018/9/12/entrez KW - Salmonella KW - YraP KW - virulence JF - Infection and immunity JO - Infect Immun VL - 86 IS - 11 N2 - Mutations in σE-regulated lipoproteins have previously been shown to impact bacterial viability under conditions of stress and during in vivo infection. YraP is conserved across a number of Gram-negative pathogens, including Neisseria meningitidis, where the homolog is a component of the Bexsero meningococcal group B vaccine. Investigations using laboratory-adapted Escherichia coli K-12 have shown that yraP mutants have elevated sensitivity to a range of compounds, including detergents and normally ineffective antibiotics. In this study, we investigate the role of the outer membrane lipoprotein YraP in the pathogenesis of Salmonella enterica serovar Typhimurium. We show that mutations in S Typhimurium yraP result in a defective outer membrane barrier with elevated sensitivity to a range of compounds. This defect is associated with attenuated virulence in an oral infection model and during the early stages of systemic infection. We show that this attenuation is not a result of defects in lipopolysaccharide and O-antigen synthesis, changes in outer membrane protein levels, or the ability to adhere to and invade eukaryotic cell lines in vitro. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/30201701/YraP_Contributes_to_Cell_Envelope_Integrity_and_Virulence_of_Salmonella_enterica_Serovar_Typhimurium_ L2 - http://iai.asm.org/cgi/pmidlookup?view=long&pmid=30201701 DB - PRIME DP - Unbound Medicine ER -