title: Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling.
abstract: Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling.
authors: National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
authors: Nicolae
authors: N
authors: Corcionivoschi
authors: Luis A J
authors: LA
authors: Alvarez
authors: Thomas H
authors: TH
authors: Sharp
authors: Monika
authors: M
authors: Strengert
authors: Abofu
authors: A
authors: Alemka
authors: Judith
authors: J
authors: Mantell
authors: Paul
authors: P
authors: Verkade
authors: Ulla G
authors: UG
authors: Knaus
authors: Billy
authors: B
authors: Bourke
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D016123:Campylobacter jejuni / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D020134:Catalytic Domain; D000074623:Dual Oxidases; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D008969:Molecular Sequence Data; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000378:metabolism; D009924:Organ Culture Techniques; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014534:UDPglucose 4-Epimerase / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D017382:Reactive Oxygen Species; D019000:Phosphotyrosine; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C431515:DUOX2 protein, human; D011505:Protein-Tyrosine Kinases; D014534:UDPglucose 4-Epimerase