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Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion Europe PMC Funders Group

Abstract : Pseudomonas aeruginosa is a Gram-negative bacterial pathogen associated with acute and chronic infections. The universal c-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 identified an unrecognized SadC partner, WarA, which we show is a methyltransferase in complex with a putative kinase WarB. We established that WarA binds to c-di-GMP, which potentiates its methyltransferase activity. Together, WarA and WarB have structural similarities with the bi-functional Escherichia coli 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. Pseudomonas aeruginosa is a Gram-negative bacterial pathogen commonly associated with the cystic fibrosis (CF) lung. Upon infection, a switch occurs between two contrasting modes of bacterial growth. Acute infection is characterised by a planktonic lifestyle whereby P. aeruginosa is motile and induces the type III secretion system (T3SS). The transition to chronic infection coincides with a P. aeruginosa behavioural switch to a sessile lifestyle, Author contributions. AF and RMC conceived and designed experiments, and wrote the paper. JSL and YH contributed materials including anti-LPS monoclonal antibodies, performed LPS analysis and helped with editing of the manuscript. JAM and CB performed the bacterial two-hybrid screen. MJMM and SM contributed zebrafish experiments. RMC conducted all experiments.
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Ronan Mccarthy, Maria Mazon-Moya, Joana Moscoso, Youai Hao, Joseph Lam, et al.. Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion Europe PMC Funders Group. Nature Microbiology, Nature Publishing Group, 2017, 2, pp.17027. ⟨10.1038/nmicrobiol.2017.27⟩. ⟨hal-01770229⟩

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