PUBLICATION
Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion
- Authors
- McCarthy, R.R., Mazon-Moya, M.J., Moscoso, J.A., Hao, Y., Lam, J.S., Bordi, C., Mostowy, S., Filloux, A.
- ID
- ZDB-PUB-170307-4
- 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
Citation
McCarthy, R.R., Mazon-Moya, M.J., Moscoso, J.A., Hao, Y., Lam, J.S., Bordi, C., Mostowy, S., Filloux, A. (2017) Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion. Nature microbiology. 2:17027.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping