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Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion

Title: Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion
Authors: McCarthy, RR
Mazon-Moya, MJ
Moscoso, JA
Hao, Y
Lam, JS
Bordi, C
Mostowy, S
Filloux, A
Item Type: Journal Article
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.
Issue Date: 6-Mar-2017
Date of Acceptance: 31-Jan-2017
URI: http://hdl.handle.net/10044/1/65679
DOI: https://dx.doi.org/10.1038/nmicrobiol.2017.27
ISSN: 2058-5276
Publisher: Nature Research
Journal / Book Title: Nature Microbiology
Volume: 2
Issue: 6
Copyright Statement: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/L007959/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
ESCHERICHIA-COLI O9A
O-ANTIGEN
POLYACRYLAMIDE-GELS
DIGUANYLIC ACID
CHAIN-LENGTH
INFECTION
ZEBRAFISH
VIRULENCE
PROTEIN
DOMAIN
Animals
Cyclic GMP
Disease Models, Animal
Immune Evasion
Lipopolysaccharides
Methyltransferases
Protein Binding
Pseudomonas Infections
Pseudomonas aeruginosa
Zebrafish
Publication Status: Published
Article Number: ARTN 17027
Appears in Collections:Department of Medicine
Faculty of Medicine
Faculty of Natural Sciences



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