Journal articles
Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion Europe PMC Funders Group
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.
Cited literature [64 references]
https://hal-amu.archives-ouvertes.fr/hal-01770229
Contributor : Christophe Bordi Connect in order to contact the contributor
Submitted on : Wednesday, April 18, 2018 - 5:00:34 PM
Last modification on : Tuesday, February 22, 2022 - 12:02:01 PM
Contributor : Christophe Bordi Connect in order to contact the contributor
Submitted on : Wednesday, April 18, 2018 - 5:00:34 PM
Last modification on : Tuesday, February 22, 2022 - 12:02:01 PM
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McCarty-2017.pdf
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