Resistance to antimicrobial peptides contributes to persistence of Salmonella typhimurium in the C. elegans intestine.
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 Delta pSLT 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 Delta pSLT 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.
Alegado
Rosanna A
RA
Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Tan
Man-Wah
MW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D017238:Genes, Helminth / Q000235:genetics; D044404:Genomic Islands; D007113:Immunity, Innate / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D007422:Intestines / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010455:Peptides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011112:Polymyxin B / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D015843:Serpins / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics; D037521:Virulence Factors / Q000502:physiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011112:Polymyxin B; D012097:Repressor Proteins; D015843:Serpins; D014157:Transcription Factors; D014764:Viral Proteins; D037521:Virulence Factors; C486396:abf-1 protein, C elegans; C117111:spp-1 protein, C elegans; C061064:PhoP protein, Bacteria; C086597:lambda Spi-1; C074641:interleukin-1beta-converting enzyme inhibitor