| Autor: |
McCarthy RR; MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK., Mazon-Moya MJ; Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 4AZ, UK., Moscoso JA; MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK., Hao Y; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada., Lam JS; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada., Bordi C; Laboratoire d'Ingénierie des Systèmes Macromoléculaires, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université, CNRS UMR7255, Marseille, France., Mostowy S; Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 4AZ, UK., Filloux A; MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK. |
| Abstrakt: |
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. |
