title: Killing of Candida albicans filaments by Salmonella enterica serovar Typhimurium is mediated by sopB effectors, parts of a type III secretion system.
abstract: Although bacterial-fungal interactions shape microbial virulence during polymicrobial infections, only a limited number of studies have evaluated this interaction on a genetic level. We report here that one interaction is mediated by sopB, an effector of a type III secretion system (TTSS) of Salmonella enterica serovar Typhimurium. In these studies, we screened 10 TTSS effector-related mutants and determined their role in the killing of C. albicans filaments in vitro during coinfection in planktonic environments. We found that deleting the sopB gene (which encodes inositol phosphatase) was associated with a significant decrease in C. albicans killing at 25°C after 5 days, similar to that caused by the deletion of sipB (which encodes TTSS translocation machinery components). The sopB deletion dramatically influenced the killing of C. albicans filaments. It was associated with repressed filamentation in the Caenorhabditis elegans model of C. albicans-S. Typhimurium coinfection, as well as with biofilm formation by C. albicans. We confirmed that SopB translocated to fungal filaments through SipB during coinfection. Using quantitative real-time PCR assays, we found that the Candida supernatant upregulated the S. Typhimurium genes associated with C. albicans killing (sopB and sipB). Interestingly, the sopB effector negatively regulated the transcription of CDC42, which is involved in fungal viability. Taken together, these results indicate that specific TTSS effectors, including SopB, play a critical role in bacterial-fungal interactions and are important to S. Typhimurium in order to selectively compete with fungal pathogens. These findings highlight a new role for TTSS of S. Typhimurium in the intestinal tract and may further explain the evolution and maintenance of these traits.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Younghoon
authors.initials: Y
authors.lastname: Kim
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000898:Antibiosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000254:growth & development / Q000502:physiology*; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D050296:Microbial Viability; D009154:Mutation; D021381:Protein Transport; D012486:Salmonella typhimurium / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C113620:ALS3 protein, Candida albicans; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C118102:HWP1 protein, Candida albicans; D008562:Membrane Glycoproteins; C489432:TEC1 protein, Candida albicans; D014157:Transcription Factors; C489224:SopB protein, Salmonella; D020764:cdc42 GTP-Binding Protein