TY - JOUR
T1 - Resistance to host antimicrobial peptides is necessary for Salmonella virulence
AU - Groisman, Eduardo A.
AU - Parra-Lopez, Carlos
AU - Salcedo, Margarita
AU - Lipps, Craig J.
AU - Heffron, Fred
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - Cecropin
KW - Defensin
KW - Magainin
KW - Pathogenesis
KW - Transposon mutagenesis
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U2 - 10.1073/pnas.89.24.11939
DO - 10.1073/pnas.89.24.11939
M3 - Article
C2 - 1465423
AN - SCOPUS:0027065569
SN - 0027-8424
VL - 89
SP - 11939
EP - 11943
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24
ER -