Resistance to host antimicrobial peptides is necessary for Salmonella virulence

Eduardo A. Groisman, Carlos Parra-Lopez, Margarita Salcedo, Craig J. Lipps, Fred Heffron

    Research output: Contribution to journalArticle

    198 Scopus citations

    Abstract

    The production of antibacterial peptides is a host defense strategy used by various species, including mammals, amphibians, and insects. Successful pathogens, such as the facultative intracellular bacterium Salmonella typhimurium, have evolved resistance mechanisms to this ubiquitous type of host defense. To identify the genes required for resistance to host peptides, we isolated a library of 20,000 MudJ transposon insertion mutants of a virulent peptide-resistant S. typhimurium strain and screened it for hypersensitivity to the antimicrobial peptide protamine. Eighteen mutants had heightened susceptibility to protamine and 12 of them were characterized in detail. Eleven mutants were attenuated for virulence in vivo when inoculated into BALB/c mice by the intragastric route, and 8 of them were also avirulent following intraperitoneal inoculation. The mutants fell into different phenotypic classes with respect to their susceptibility to rabbit defensin NP-1, frog magainin 2, pig cecropin P1, and the insect venom-derived peptides mastoparan and melittin. The resistance loci mapped to eight distinct locations in the genome. Characterization of the mutants showed that one had a defective lipopolysaccharide and another mutant harbored a mutation in phoP, a locus previously shown to control expression of Salmonella virulence genes. Our data indicate that the ability to resist the killing effect of host antimicrobial peptides is a virulence property and that several resistance mechanisms operate in S. typhimurium.

    Original languageEnglish (US)
    Pages (from-to)11939-11943
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume89
    Issue number24
    DOIs
    StatePublished - Jan 1 1992

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    Keywords

    • Cecropin
    • Defensin
    • Magainin
    • Pathogenesis
    • Transposon mutagenesis

    ASJC Scopus subject areas

    • General

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