title: Identification of virulence properties in Salmonella Typhimurium DT104 using Caenorhabditis elegans.
abstract: Salmonella enterica serover Typhimurium definitive phage type DT104, resistant to multiple antibiotics, is one of the most widespread Salmonella species in human infection worldwide. Although several cohort studies indicate that DT104 carrying the multidrug resistance (MDR) locus on salmonella genomic island 1 is a possible hyper-virulent strain compared to DT104 strains without MDR, or other Salmonella enterica serotypes, existing experimental evidence regarding virulence properties associated with the MDR region is controversial. To address this question, we constructed an isogenic MDR deletion (∆MDR) mutant strain of DT104, SNS12, by allelic exchange and used Caenorhabditis elegans as a host model to assess differences in virulence between these two strains. SNS12 exhibited decreased virulence in C. elegans, and we observed increased colonization and proliferation of the intestine of C. elegans by DT104. The immune response against MDR-carrying DT104 appears to function through a non-canonical Unfolded Protein Response (UPR) pathway, namely prion-like-(QN-rich)-domain-bearing protein pathway (PQN), in a ced-1 dependent manner in C. elegans. Further, we also demonstrate that genes of the PQN pathway and antimicrobial peptide gene abf-2, are expressed at higher transcriptional levels in worms immediately following exposure to DT104, in comparison with worms exposed to SNS12. Altogether, our results suggest that the MDR region of Salmonella Typhimurium DT104 has a direct role in virulence against Caenorhabditis elegans.
authors.affiliation: Division of Virulence Assessment, Food and Drug Administration, Laurel, Maryland, United States of America ; Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, United States of America.
authors.forename: Surasri N
authors.initials: SN
authors.lastname: Sahu
authors.forename: Yuda
authors.initials: Y
authors.lastname: Anriany
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Grim
authors.forename: Sungji
authors.initials: S
authors.lastname: Kim
authors.forename: Zenas
authors.initials: Z
authors.lastname: Chang
authors.forename: Sam W
authors.initials: SW
authors.lastname: Joseph
authors.forename: Hediye N
authors.initials: HN
authors.lastname: Cinar
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D044404:Genomic Islands; D007422:Intestines / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C422043:ced-1 protein, C elegans