dc.contributor.author	An, Shi-Qi
dc.contributor.author	Caly, Delphine L.
dc.contributor.author	McCarthy, Yvonne
dc.contributor.author	Murdoch, Sarah L.
dc.contributor.author	Ward, Joseph
dc.contributor.author	Febrer, Melanie
dc.contributor.author	Dow, J. Maxwell
dc.contributor.author	Ryan, Robert P.
dc.contributor.funder	Wellcome Trust, United Kingdom
dc.date.accessioned	2016-02-17T11:43:38Z
dc.date.available	2016-02-17T11:43:38Z
dc.date.issued	2014
dc.description.abstract	Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.	en
dc.description.sponsorship	Wellcome Trust, United Kingdom (WT093314MA; WT100204AIA)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	e1004429
dc.identifier.citation	An S-q, Caly DL, McCarthy Y, Murdoch SL, Ward J, Febrer M, et al. (2014) Novel Cyclic di-GMP Effectors of the YajQ Protein Family Control Bacterial Virulence. PLoS Pathog 10(10): e1004429. doi:10.1371/journal.ppat.1004429
dc.identifier.doi	10.1371/journal.ppat.1004429
dc.identifier.issn	1553-7366
dc.identifier.issued	10	en
dc.identifier.journaltitle	PLOS PATHOGENS	en
dc.identifier.uri	https://hdl.handle.net/10468/2322
dc.identifier.volume	10	en
dc.language.iso	en	en
dc.publisher	Public Library of Science	en
dc.rights	© 2015 An et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.subject	PilZ domain proteins	en
dc.subject	Campestris pv. campestris	en
dc.subject	Diffusible signal factor	en
dc.subject	Airway epithelial cells	en
dc.subject	Cystic fibrosis airway	en
dc.subject	Xanthomonas campestris	en
dc.subject	Pseudomonas aeruginosa	en
dc.subject	HD-GYP	en
dc.subject	Biofilm formation	en
dc.subject	2nd messenger	en
dc.title	Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence	en
dc.type	Article (peer-reviewed)	en

Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

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