title: Thioredoxin 1 participates in the activity of the Salmonella enterica serovar Typhimurium pathogenicity island 2 type III secretion system.
abstract: The facultative intracellular pathogen Salmonella enterica serovar Typhimurium relies on its Salmonella pathogenicity island 2 (SPI2) type III secretion system (T3SS) for intracellular replication and virulence. We report that the oxidoreductase thioredoxin 1 (TrxA) and SPI2 are coinduced for expression under in vitro conditions that mimic an intravacuolar environment, that TrxA is needed for proper SPI2 activity under these conditions, and that TrxA is indispensable for SPI2 activity in both phagocytic and epithelial cells. Infection experiments in mice demonstrated that SPI2 strongly contributed to virulence in a TrxA-proficient background whereas SPI2 did not affect virulence in a trxA mutant. Complementation analyses using wild-type trxA or a genetically engineered trxA coding for noncatalytic TrxA showed that the catalytic activity of TrxA is essential for SPI2 activity in phagocytic cells whereas a noncatalytic variant of TrxA partially sustained SPI2 activity in epithelial cells and virulence in mice. These results show that TrxA is needed for the intracellular induction of SPI2 and provide new insights into the functional integration between catalytic and noncatalytic activities of TrxA and a bacterial T3SS in different settings of intracellular infections.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden.
authors.forename: Aurel
authors.initials: A
authors.lastname: Negrea
authors.forename: Eva
authors.initials: E
authors.lastname: Bjur
authors.forename: Speranta
authors.initials: S
authors.lastname: Puiac
authors.forename: Sofia Eriksson
authors.initials: SE
authors.lastname: Ygberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Aslund
authors.forename: Mikael
authors.initials: M
authors.lastname: Rhen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004285:Dogs; D005260:Female; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D044404:Genomic Islands / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; C440638:SPI-2 protein, Salmonella; D013879:Thioredoxins