Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion.
Ronan R McCarthyMaria J Mazon-MoyaJoana A MoscosoYouai HaoJoseph S LamChristophe BordiSerge MostowyAlain FillouxPublished in: Nature microbiology (2017)
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.
Keyphrases
- biofilm formation
- pseudomonas aeruginosa
- inflammatory response
- cystic fibrosis
- gram negative
- escherichia coli
- candida albicans
- toll like receptor
- immune response
- multidrug resistant
- lps induced
- anti inflammatory
- acinetobacter baumannii
- staphylococcus aureus
- lung function
- metabolic syndrome
- liver failure
- physical activity
- cardiovascular disease
- drug induced
- weight loss
- respiratory failure
- dendritic cells
- type diabetes
- drug resistant
- transcription factor
- tyrosine kinase