ZFIN ID: ZDB-PUB-170307-4
Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion
McCarthy, R.R., Mazon-Moya, M.J., Moscoso, J.A., Hao, Y., Lam, J.S., Bordi, C., Mostowy, S., Filloux, A.
Date: 2017
Source: Nature microbiology   2: 17027 (Journal)
Registered Authors: Mostowy, Serge
Keywords: Bacterial immune evasion, Bacterial pathogenesis, Bacterial physiology, Biofilms, Pathogens
MeSH Terms:
  • Animals
  • Cyclic GMP/analogs & derivatives*
  • Cyclic GMP/metabolism
  • Disease Models, Animal
  • Immune Evasion*
  • Lipopolysaccharides/metabolism*
  • Methyltransferases/metabolism
  • Protein Binding
  • Pseudomonas Infections/microbiology
  • Pseudomonas Infections/pathology
  • Pseudomonas aeruginosa/metabolism*
  • Pseudomonas aeruginosa/pathogenicity*
  • Zebrafish
PubMed: 28263305 Full text @ Nat Microbiol
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.