title: Lipopolysaccharide Phosphorylation by the WaaY Kinase Affects the Susceptibility of Escherichia coli to the Human Antimicrobial Peptide LL-37.
abstract: The human cathelicidin LL-37 is a multifunctional host defense peptide with immunomodulatory and antimicrobial roles. It kills bacteria primarily by altering membrane barrier properties, although the exact sequence of events leading to cell lysis has not yet been completely elucidated. Random insertion mutagenesis allowed isolation of Escherichia coli mutants with altered susceptibility to LL-37, pointing to factors potentially relevant to its activity. Among these, inactivation of the waaY gene, encoding a kinase responsible for heptose II phosphorylation in the LPS inner core, leads to a phenotype with decreased susceptibility to LL-37, stemming from a reduced amount of peptide binding to the surface of the cells, and a diminished capacity to lyse membranes. This points to a specific role of the LPS inner core in guiding LL-37 to the surface of Gram-negative bacteria. Although electrostatic interactions are clearly relevant, the susceptibility of the waaY mutant to other cationic helical cathelicidins was unaffected, indicating that particular structural features or LL-37 play a role in this interaction.
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Karol
authors.initials: K
authors.lastname: Bociek
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferluga
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Mardirossian
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Benincasa
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tossi
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Gennaro
authors.affiliation: From the Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy mscocchi@units.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Scocchi
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D054804:Cathelicidins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D006539:Heptoses / Q000737:chemistry / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity
chemical_list: D023181:Antimicrobial Cationic Peptides; C102359:BMAP-27; C481640:Bac7(1-35) peptide; D001798:Blood Proteins; C000594016:CRAMP (16-33); D054804:Cathelicidins; D029968:Escherichia coli Proteins; D006539:Heptoses; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011506:Proteins; C403305:SMAP29 protein, Ovis aries
keywords: antimicrobial peptide (AMP); cell permeabilization; lipopolysaccharide; lipopolysaccharide (LPS); phosphorylation; transposable element (TE)