ArticleThe Journal of biological chemistry2015
Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 103 citations in OpenAlex.
- Linking the second messenger cyclic di-GMP signaling with the regulatory activity of the small RNA ErsA in Pseudomonas aeruginosa.Nucleic acids research · 2026Article
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- Biological and clinical significance of iron inJournal of bacteriology · 2026Review
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- UnderstandingMicroorganisms · 2026Review
- Cyclic-di-GMP interferes with DNA-MucR-DNA bridging to derepress genes targeted by the xenogeneic silencer MucR.Nucleic acids research · 2025Article
- Pseudomonas aeruginosa biofilm: treatment strategies to combat infection.Archives of microbiology · 2025Review
- The c-di-GMP effector FleQ controls alginate production by repressing transcription ofMicrobiology (Reading, England) · 2025Article
- Insertion of a Divergent GAF-like Domain Defines a Novel Family of YcgR Homologues That Bind c-di-GMP inACS omega · 2025Article
- Thermal shift assay to identify ligands for bacterial sensor proteins.FEMS microbiology reviews · 2025Review
- Advances in alginate biosynthesis: regulation and production inFrontiers in bioengineering and biotechnology · 2025Review
- Busulfan inhibitsFrontiers in cellular and infection microbiology · 2025Article
- Bacterial c-di-GMP triggers metamorphosis of mussel larvae through a STING receptor.NPJ biofilms and microbiomes · 2024Article
- Flip the switch: the role of FleQ in modulating the transition between the free-living and sessile mode of growth inJournal of bacteriology · 2024Review
- Diversity of biofilm-specific antimicrobial resistance genes inIranian journal of microbiology · 2023Article
- Pseudomonas aeruginosa biofilm exopolysaccharides: assembly, function, and degradation.FEMS microbiology reviews · 2023Review
- Genomic insights into the c-di-GMP signaling and biofilm development in the saprophytic spirochete Leptospira biflexa.Archives of microbiology · 2023Article
- Challenges in using transcriptome data to study the c-di-GMP signaling network inFEMS microbes · 2023Article
- Structure of the AlgKX modification and secretion complex required for alginate production and biofilm attachment in Pseudomonas aeruginosa.Nature communications · 2022Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.