title: Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion.
abstract: Pseudomonas aeruginosa is a Gram-negative bacterial pathogen associated with acute and chronic infections. The universal cyclic-di-GMP second messenger is instrumental in the switch from a motile lifestyle to resilient biofilm as in the cystic fibrosis lung. The SadC diguanylate cyclase is associated with this patho-adaptive transition. Here, we identify an unrecognized SadC partner, WarA, which we show is a methyltransferase in complex with a putative kinase, WarB. We established that WarA binds to cyclic-di-GMP, which potentiates its methyltransferase activity. Together, WarA and WarB have structural similarities with the bifunctional Escherichia coli lipopolysaccharide (LPS) O antigen regulator WbdD. Strikingly, WarA influences P. aeruginosa O antigen modal distribution and interacts with the LPS biogenesis machinery. LPS is known to modulate the immune response in the host, and by using a zebrafish infection model, we implicate WarA in the ability of P. aeruginosa to evade detection by the host.
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Ronan R
authors.initials: RR
authors.lastname: McCarthy
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 4AZ, UK.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Mazon-Moya
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Joana A
authors.initials: JA
authors.lastname: Moscoso
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Youai
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Lam
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université, CNRS UMR7255, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bordi
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 4AZ, UK.
authors.forename: Serge
authors.initials: S
authors.lastname: Mostowy
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Alain
authors.identifier: http://orcid.org/0000-0003-1307-0289
authors.initials: A
authors.lastname: Filloux
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D057131:Immune Evasion; D008070:Lipopolysaccharides / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism; D011485:Protein Binding; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000378:metabolism* / Q000472:pathogenicity*; D015027:Zebrafish
chemical_list: D008070:Lipopolysaccharides; C062025:bis(3',5')-cyclic diguanylic acid; D008780:Methyltransferases; D006152:Cyclic GMP