title: Influence of lipopolysaccharide outer-core in the intrinsic resistance to antimicrobial peptides and virulence in Edwardsiella ictaluri.
abstract: The genus Edwardsiella consists of bacteria with an intrinsic resistance to cyclic cationic antimicrobial peptides (CAMPs). Edwardsiella ictaluri, a pathogen of the catfish (Ictalurus punctatus) and the causative agent of a systemic infection, is highly resistant to CAMPs. Previously, we determined that the oligo-polysaccharide (O-PS) of the lipopolysaccharide (LPS) does not play a role in the E. ictaluri CAMP resistance and an intact core-lipid A structure is necessary for CAMPs resistance. Here, we evaluated the influence of the outer-core in the CAMPs resistance and fish virulence. E. ictaluri wabG, a gene that encodes for the UDP-glucuronic acid transferase that links the lipid A-inner-core to the outer-core-oligopolysaccharides, was deleted. Deletion of ΔwabG caused a pleiotropic effect, influencing LPS synthesis, CAMPs resistance, growth, and biofilm formation. E. ictaluri ΔwabG was attenuated in zebrafish indicating the important role of LPS during fish pathogenesis. Also, we evaluated the inflammatory effects of wabG LPS in catfish ligated loop model, showing a decreased inflammatory effect at the gut level respects to the E. ictaluri wild type. We conclude that E. ictaluri CAMPs resistance is related to the molecules present in the LPS outer-core and that fish gut inflammation triggered by E. ictaluri is LPS dependent, reinforcing the hypothesis that fish gut recognizes LPS in an O-PS dependent fashion.
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Life and Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Martin
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; Microbial Pathogenesis and Vaccinology Research Group, Faculty of Sciences, Universidad Mayor, Huechuraba 8580745, Chile.
authors.forename: Ignacia
authors.initials: I
authors.lastname: Diaz
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Kilbourne
authors.affiliation: Microbial Pathogenesis and Vaccinology Research Group, Faculty of Sciences, Universidad Mayor, Huechuraba 8580745, Chile.
authors.forename: Oscar
authors.initials: O
authors.lastname: Almarza
authors.affiliation: Microbial Pathogenesis and Vaccinology Research Group, Faculty of Sciences, Universidad Mayor, Huechuraba 8580745, Chile; PhD Program in Integrative Genomics, Faculty of Sciences, Universidad Mayor, Huechuraba 8580745, Chile.
authors.forename: Cristopher
authors.initials: C
authors.lastname: Segovia
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Life and Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Life and Sciences, Arizona State University, Tempe, AZ 85287, USA; Microbial Pathogenesis and Vaccinology Research Group, Faculty of Sciences, Universidad Mayor, Huechuraba 8580745, Chile. Electronic address: jasantanderm@asu.edu.
authors.forename: Javier
authors.initials: J
authors.lastname: Santander
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020610:Edwardsiella ictaluri / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000662:veterinary*; D005393:Fish Diseases / Q000382:microbiology*; D007059:Ictaluridae; D008070:Lipopolysaccharides / Q000378:metabolism*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014774:Virulence; D015027:Zebrafish
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides
keywords: Edwardsiella; Fish virulence; Glucuronic acid transferase; O-polysaccharide