title: The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence.
abstract: Pathogenic micro-organisms have evolved many strategies to counteract the antimicrobial peptides (AMPs) that they encounter upon entry into host systems. These strategies play vital roles in the virulence of pathogenic micro-organisms. The Salmonella enterica serovar Typhimurium genome has a gene cluster consisting of yejA, yejB, yejE and yejF genes, which encode a putative ATP-binding cassette (ABC) transporter. Our study shows that these genes constitute an operon. We deleted the yejF gene, which encodes the ATPase component of the putative ABC transporter. The DeltayejF strain showed increased sensitivity to protamine, melittin, polymyxin B, human defensin (HBD)-1 and HBD-2, and was compromised in its capacity to proliferate inside activated macrophages and epithelial cells. Inside Intestine 407 cells, Salmonella was found to co-localize with human defensins HD-5 and HBD-1; this suggests that the ability to counteract AMPs in the intracellular milieu is important for Salmonella. In a murine typhoid model, the DeltayejF strain displayed decreased virulence when infected intragastrically. These findings suggest that the putative transporter encoded by the yejABEF operon is involved in counteracting AMPs, and that it contributes to the virulence of Salmonella.
authors.affiliation: Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Sandeepa M
authors.initials: SM
authors.lastname: Eswarappa
authors.affiliation: Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Panguluri
authors.affiliation: Institute of Clinical Microbiology, Immunology and Hygiene, FAU Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hensel
authors.affiliation: Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004261:DNA Replication; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000235:genetics; D018613:Microscopy, Confocal; D009876:Operon; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D012475:Salmonella / Q000235:genetics; D019779:Salmonella enterica / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D017384:Sequence Deletion; D017385:Sequence Homology; D014158:Transcription, Genetic; D015854:Up-Regulation; D014774:Virulence; D023084:alpha-Defensins / Q000032:analysis; D023083:beta-Defensins / Q000032:analysis
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; C500225:DEFA5 protein, human; C406407:DEFB1 protein, human; D010455:Peptides; D012333:RNA, Messenger; D023084:alpha-Defensins; D023083:beta-Defensins