title: Role of uropathogenic Escherichia coli OmpT in the resistance against human cathelicidin LL-37.
abstract: Uropathogenic Escherichia coli (UPEC) strains are among the most prevalent causative agents of urinary tract infections. To establish infection, UPEC must overcome the bactericidal action of host antimicrobial peptides. Previously, the enterohaemorrhagic E. coli outer membrane protease, OmpT, was shown to degrade and inactivate the human antimicrobial peptide LL-37. This study aims to investigate the involvement of UPEC OmpT in LL-37 degradation. An ompT deletion mutant was generated in the prototypical UPEC strain CFT073. Western blot analysis showed that the OmpT protein level is moderate in CFT073. In agreement, OmpT was shown to partially cleave LL-37. However, no difference in the minimum inhibitory concentration of LL-37 was observed between CFT073 and the ompT mutant. Plasmid complementation of ompT, which led to increased OmpT levels, resulted in complete cleavage of LL-37 and a fourfold increase in the minimum inhibitory concentration. The analysis of other UPEC isolates showed similar OmpT activity levels as CFT073. Although UPEC OmpT can cleave LL-37, we conclude that the low level of OmpT limits its contribution to LL-37 resistance. Collectively, these data suggest that UPEC OmpT is likely accompanied by other LL-37 resistance mechanisms.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Brannon
authors.forename: Jenny-Lee
authors.initials: JL
authors.lastname: Thomassin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desloges
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Moual
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D056689:Uropathogenic Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; C499588:ompT protein, E coli; D010447:Peptide Hydrolases; D054804:Cathelicidins
keywords: antimicrobial peptide; cathelicidin; outer membrane protease; urinary tract infection; uropathogenic Escherichia coli