ArticleBMC microbiology2014
A systematic analysis of the in vitro and in vivo functions of the HD-GYP domain proteins of Vibrio cholerae.
Article in BMC microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Roles of divalent metals in the regulation of cyclic di-GMP signaling in bacteria.Journal of bacteriology · 2026Review
- Structural analyses uncover protease-adhesin interactions and c-di-GMP receptor regulation in sulfate-reducing bacteria.Nature communications · 2026Article
- Two-component systems in Vibrio species: Regulation of virulence and implications for therapeutic development.Folia microbiologica · 2026Review
- Discovery of Novel c-di-GMP-Related Genes inPathogens (Basel, Switzerland) · 2026Article
- Review
- A comparative genomic and phenotypic study ofMicrobiology (Reading, England) · 2024Article
- Article
- The Vibrio cholerae master regulator for the activation of biofilm biogenesis genes, VpsR, senses both cyclic di-GMP and phosphate.Nucleic acids research · 2022Article
- Disruption of c-di-GMP Signaling Networks Unlocks Cryptic Expression of Secondary Metabolites during Biofilm Growth inApplied and environmental microbiology · 2022Article
- Sequence Conservation, Domain Architectures, and Phylogenetic Distribution of the HD-GYP Type c-di-GMP Phosphodiesterases.Journal of bacteriology · 2022Review
- HD-[HD-GYP] Phosphodiesterases: Activities and Evolutionary Diversification within the HD-GYP Family.Biochemistry · 2020Article
- Functional Specialization inmBio · 2019Article
- A Subset of Exoribonucleases Serve as Degradative Enzymes for pGpG in c-di-GMP Signaling.Journal of bacteriology · 2018Article
- The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation.Journal of bacteriology · 2017Article
- Progress in Understanding the Molecular Basis Underlying Functional Diversification of Cyclic Dinucleotide Turnover Proteins.Journal of bacteriology · 2017Review
- Cyclic diguanylate signaling in Gram-positive bacteria.FEMS microbiology reviews · 2016Review
- Two nucleotide second messengers regulate the production of the Vibrio cholerae colonization factor GbpA.BMC microbiology · 2015Article
- Structural basis of functional diversification of the HD-GYP domain revealed by the Pseudomonas aeruginosa PA4781 protein, which displays an unselective bimetallic binding site.Journal of bacteriology · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe second messenger cyclic diguanylate (c-di-GMP) plays a central role in bacterial adaptation to extracellular stimuli, controlling processes such as motility, biofilm development, cell development and, in some pathogens, virulence. The intracellular level of c-di-GMP is controlled by the complementary activities of diguanylate cyclases containing a GGDEF domain and two classes of c-di-GMP phosphodiesterases containing an EAL or HD-GYP hydrolytic domain. Compared to the GGDEF and EAL domains, the functions of HD-GYP domain family proteins are poorly characterized. The human diarrheal pathogen Vibrio cholerae encodes nine putative HD-GYP domain proteins. To determine the contributions of HD-GYP domain proteins to c-di-GMP signaling in V. cholerae, we systematically analyzed the enzymatic functionality of each protein and their involvement in processes known to be regulated by c-di-GMP: motility, biofilm development and virulence.
resultsComplementary in vitro and in vivo experiments showed that four HD-GYP domain proteins are active c-di-GMP phosphodiesterases: VC1295, VC1348, VCA0210 and VCA0681. Mutation of individual HD-GYP domain genes, as well as combinatorial mutations of multiple HD-GYP domain genes, had no effect on motility or biofilm formation of V. cholerae under the conditions tested. Furthermore, no single HD-GYP domain gene affected intestinal colonization by V. cholerae in an infant mouse model. However, inactivation of multiple HD-GYP domain genes, including the four encoding functional phosphodiesterases, significantly attenuated colonization.
conclusionsThese results indicate that the HD-GYP family of c-di-GMP phosphodiesterases impacts signaling by this second messenger during infection. Altogether, this work greatly furthers the understanding of this important family of c-di-GMP metabolic enzymes and demonstrates a role for HD-GYP domain proteins in the virulence of V. cholerae.
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