ArticleProceedings of the National Academy of Sciences of the United States of America2016
Structures of the activator of K. pneumonia biofilm formation, MrkH, indicates PilZ domains involved in c-di-GMP and DNA binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Cyclic di-GMP directly reprograms the multidrug resistance machinery via UspG-mediated sequestration of RamR in Klebsiella.PLoS pathogens · 2026Article
- Antibiofilm Activity of Three Essential Oils Against ESBL-ProducingAntibiotics (Basel, Switzerland) · 2026Article
- Rapid evolution of Klebsiella pneumoniae biofilms in vitro delineates adaptive changes selected during infection.Nature communications · 2026Article
- Discovery of Novel c-di-GMP-Related Genes inPathogens (Basel, Switzerland) · 2026Article
- Chemical inhibition of MrkH-dependent activation of type 3 fimbriae synthesis and biofilm formation by Klebsiella pneumoniae.NPJ biofilms and microbiomes · 2025Article
- Dynamic Executors of Bacterial Signals: Functional Versatility and Regulatory Networks of c-di-GMP Effectors.Biomolecules · 2025Review
- Article
- Characterization of genome-wide transpositions induced by colistin exposure in multi-drug-resistantAntimicrobial agents and chemotherapy · 2025Article
- Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.PLoS pathogens · 2025Article
- Sucrose reduces biofilm formation byBiofilm · 2025Article
- Article
- How c-di-GMP controls progression through the Streptomyces life cycle.Current opinion in microbiology · 2024Review
- Review
- A genetically encoded fluorescent biosensor for sensitive detection of cellular c-di-GMP levels inFrontiers in chemistry · 2024Article
- Dual Regulatory Role Exerted by Cyclic Dimeric GMP To Control FsnR-Mediated Bacterial Swimming.mBio · 2022Article
- Cyclic di-GMP modulates sessile-motile phenotypes and virulence in Dickeya oryzae via two PilZ domain receptors.Molecular plant pathology · 2022Article
- The Vibrio cholerae master regulator for the activation of biofilm biogenesis genes, VpsR, senses both cyclic di-GMP and phosphate.Nucleic acids research · 2022Article
- Signaling events that occur when cells ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- PlzA is a bifunctional c-di-GMP biosensor that promotes tick and mammalian host-adaptation of Borrelia burgdorferi.PLoS pathogens · 2021Article
- The World of Cyclic Dinucleotides in Bacterial Behavior.Molecules (Basel, Switzerland) · 2020Review
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2 authors.
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Abstract
The pathogenesis of Klebsiella pneumonia is linked to the bacteria's ability to form biofilms. Mannose-resistant Klebsiella-like (Mrk) hemagglutinins are critical for K pneumonia biofilm development, and the expression of the genes encoding these proteins is activated by a 3',5'-cyclic diguanylic acid (c-di-GMP)-regulated transcription factor, MrkH. To gain insight into MrkH function, we performed structural and biochemical analyses. Data revealed MrkH to be a monomer with a two-domain architecture consisting of a PilZ C-domain connected to an N domain that unexpectedly also harbors a PilZ-like fold. Comparison of apo- and c-di-GMP-bound MrkH structures reveals a large 138° interdomain rotation that is induced by binding an intercalated c-di-GMP dimer. c-di-GMP interacts with PilZ C-domain motifs 1 and 2 (RxxxR and D/NxSxxG) and a newly described c-di-GMP-binding motif in the MrkH N domain. Strikingly, these c-di-GMP-binding motifs also stabilize an open state conformation in apo MrkH via contacts from the PilZ motif 1 to residues in the C-domain motif 2 and the c-di-GMP-binding N-domain motif. Use of the same regions in apo structure stabilization and c-di-GMP interaction allows distinction between the states. Indeed, domain reorientation by c-di-GMP complexation with MrkH, which leads to a highly compacted structure, suggests a mechanism by which the protein is activated to bind DNA. To our knowledge, MrkH represents the first instance of specific DNA binding mediated by PilZ domains. The MrkH structures also pave the way for the rational design of inhibitors that target K pneumonia biofilm formation.
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