title: Mechanisms of intrinsic resistance to antimicrobial peptides of Edwardsiella ictaluri and its influence on fish gut inflammation and virulence.
abstract: The genus Edwardsiella comprises a genetically distinct taxon related to other members of the family Enterobacteriaceae. It consists of bacteria differing strongly in their biochemical and physiological features, natural habitats, and pathogenic properties. Intrinsic resistance to cationic antimicrobial peptides (CAMPs) is a specific property of the genus Edwardsiella. In particular, Edwardsiella ictaluri, an important pathogen of the catfish (Ictalurus punctatus) aquaculture and the causative agent of a fatal systemic infection, is highly resistant to CAMPs. E. ictaluri mechanisms of resistance to CAMPs are unknown. We hypothesized that E. ictaluri lipopolysaccharide (LPS) plays a role in both virulence and resistance to CAMPs. The putative genes related to LPS oligo-polysaccharide (O-PS) synthesis were in-frame deleted. Individual deletions of wibT, gne and ugd eliminated synthesis of the O-PS, causing auto-agglutination, rough colonies, biofilm-like formation and motility defects. Deletion of ugd, the gene that encodes the UDP-glucose dehydrogenase enzyme responsible for synthesis of UDP-glucuronic acid, causes sensitivity to CAMPs, indicating that UDP-glucuronic acid and its derivatives are related to CAMP intrinsic resistance. E. ictaluri OP-S mutants showed different levels of attenuation, colonization of lymphoid tissues and immune protection in zebrafish (Danio rerio) and catfish. Orally inoculated catfish with O-PS mutant strains presented different degrees of gut inflammation and colonization of lymphoid tissues. Here we conclude that intrinsic resistance to CAMPs is mediated by Ugd enzyme, which has a pleiotropic effect in E. ictaluri influencing LPS synthesis, motility, agglutination, fish gut inflammation and virulence.
authors.affiliation: Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Santander
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Martin
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Loh
authors.affiliation: Department of Wildlife and Fisheries Sciences, Texas A&M University System, College Station, TX 77843, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Pohlenz
authors.affiliation: Intercollegiate Faculty of Nutrition, Texas A&M University System, College Station, TX 77843, USA.|Department of Wildlife and Fisheries Sciences, Texas A&M University System, College Station, TX 77843, USA.
authors.forename: Delbert M
authors.initials: DM
authors.lastname: Gatlin
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.|Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D017756:Aquaculture; D002397:Catfishes / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D020610:Edwardsiella ictaluri / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D005393:Fish Diseases / Q000276:immunology / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D023181:Antimicrobial Cationic Peptides; D014533:Uridine Diphosphate Glucose Dehydrogenase