Resistance to antimicrobial peptides contributes to persistence of Salmonella typhimurium in the C. elegans intestine

• Published in: Cellular microbiology Vol. 10; no. 6; pp. 1259 - 1273
• Main Authors: Alegado, Rosanna A, Tan, Man-Wah
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.06.2008; Blackwell Publishing Ltd; Hindawi Limited
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - physiology; Basic Helix-Loop-Helix Transcription Factors - genetics; Caenorhabditis elegans - chemistry; Caenorhabditis elegans - genetics; Caenorhabditis elegans - microbiology; Caenorhabditis elegans Proteins - genetics; Genes, Helminth - genetics; Genomic Islands; Immunity, Innate - genetics; Intercellular Signaling Peptides and Proteins; Intestines - microbiology; Microbial Sensitivity Tests; Mutation; Peptides - genetics; Plasmids - genetics; Polymyxin B - pharmacology; Repressor Proteins - genetics; Salmonella Infections, Animal - immunology; Salmonella Infections, Animal - microbiology; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; Salmonella typhimurium - growth & development; Salmonella typhimurium - pathogenicity; Serpins - genetics; Transcription Factors - physiology; Viral Proteins - genetics; Virulence Factors - physiology
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2008.01124.x

The human pathogen Salmonella typhimurium can colonize, proliferate and persist in the intestine causing enteritis in mammals and mortality in the nematode Caenorhabditis elegans. Using C. elegans as a model, we determined that the Salmonella pathogenicity islands-1 and -2 (SPI-1 and SPI-2), PhoP and the virulence plasmid are required for the establishment of a persistent infection. We observed that the PhoP regulon, SPI-1, SPI-2 and spvR are induced in C. elegans and isogenic strains lacking these virulence factors exhibited significant defects in the ability to persist in the worm intestine. Salmonella infection also leads to induction of two C. elegans antimicrobial genes, abf-2 and spp-1, which act to limit bacterial proliferation. The SPI-2, phoP and ΔpSLT mutants are more sensitive to the cationic peptide polymyxin B, suggesting that resistance to worm's antimicrobial peptides might be necessary for Salmonella to persist in the C. elegans intestine. Importantly, we showed that the persistence defects of the SPI-2, phoP and ΔpSLT mutants could be rescued in vivo when expression of C. elegans spp-1 was reduced by RNAi. Together, our data suggest that resistance to host antimicrobials in the intestinal lumen is a key mechanism for Salmonella persistence.