Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria DOI Creative Commons
Tino Krell, Elizabet Monteagudo‐Cascales, Vadim M. Gumerov

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 16, 2023

Abstract Purines and their derivatives are key molecules for controlling intracellular energy homeostasis nucleotide synthesis. In eukaryotes, including humans, purines also act as signaling that mediate extracellular communication control cellular processes, such proliferation, migration, differentiation, apoptosis. However, the role of in bacteria is largely unknown. Here, by combining structural sequence information, we define a purine-binding motif, which present sensor domains thousands bacterial receptors modulate motility, gene expression, metabolism second messenger turnover. The screening compound libraries microcalorimetric titrations selected validated ability to specifically bind purine derivatives. physiological relevance sensing was demonstrated system modulates c-di-GMP levels.

Language: Английский

Bacterial sensor evolved by decreasing complexity DOI Creative Commons
Elizabet Monteagudo‐Cascales, J.A. Gavira, Jiawei Xing

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(5)

Published: Jan. 29, 2025

Bacterial receptors feed into multiple signal transduction pathways that regulate a variety of cellular processes including gene expression, second messenger levels, and motility. Receptors are typically activated by binding to ligand-binding domains (LBDs). Cache omnipresent LBDs found in bacteria, archaea, eukaryotes, humans. They form the predominant family extracytosolic bacterial were identified all major receptor types. composed either single (sCache) or double (dCache) structural module. The functional relevance bimodular remains poorly understood. Here, we identify PacF chemoreceptor phytopathogen Pectobacterium atrosepticum recognizes formate at membrane-distal module its dCache domain, triggering chemoattraction. We further demonstrate formate-specific sCache has evolved from exemplified PacF, losing membrane-proximal By solving high-resolution structures two members complex with formate, show molecular basis for is highly similar, despite their low sequence identity. apparent loss may be related observation bind ligands module, whereas studies have failed find bound This work advances our understanding sensing suggests evolution reducing complexity route shaping diversity.

Language: Английский

Citations

2
MiST 4.0: a new release of the microbial signal transduction database, now with a metagenomic component DOI Creative Commons
Vadim M. Gumerov,

Luke E. Ulrich,

Igor B. Zhulin

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D647 - D653

Published: Oct. 4, 2023

Abstract Signal transduction systems in bacteria and archaea link environmental stimuli to specific adaptive cellular responses. They control gene expression, motility, biofilm formation, development other processes that are vital survival. The microbial signal (MiST) database is an online resource stores tens of thousands genomes allows users explore their profiles, analyze bulk using the application programming interface (API) make testable hypotheses about functions newly identified signaling systems. However, metagenomes remained completely unexplored. To lay foundation for research metagenomic transduction, we have prepared a new release MiST database, 4.0, which features over 10 000 metagenome-assembled (MAGs), scaled representation proteins detailed BioSample information. In addition, several been processed stored database. A has developed seamlessly switch between MAGs. 4.0 freely available at https://mistdb.com; MAGs can also be explored API on same page.

Language: Английский

Citations

33
Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria DOI Creative Commons
Elizabet Monteagudo‐Cascales, Vadim M. Gumerov, Matilde Fernández

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 12, 2024

Abstract Purines and their derivatives control intracellular energy homeostasis nucleotide synthesis, act as signaling molecules. Here, we combine structural sequence information to define a purine-binding motif that is present in sensor domains of thousands bacterial receptors modulate motility, gene expression, metabolism, second-messenger turnover. Microcalorimetric titrations selected validate ability specifically bind purine derivatives, evolutionary analyses indicate sensors share common ancestor with amino-acid receptors. Furthermore, provide experimental evidence physiological relevance sensing system modulates c-di-GMP levels.

Language: Английский

Citations

8
Specificities of Chemosensory Receptors in the Human Gut Microbiota DOI Creative Commons
Wenhao Xu, Ekaterina Jalomo-Khayrova, Vadim M. Gumerov

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

The human gut is rich in metabolites and harbors a complex microbial community, yet the sensory repertoire of its commensal bacteria remains largely uncharacterized. Here we systematically mapped ligand specificities extracytoplasmic domains from twenty members microbiota, with primary focus on abundant physiologically important class Clostridia. We identified diverse as specific stimuli for three major functional classes transmembrane receptors. further characterized novel subsets sensors belonging to Cache superfamily, lactate, dicarboxylic acids, uracil short-chain fatty acids (SCFAs), respectively, investigated evolution their specificity. Structural biochemical analysis newly described dCache_1UR domain revealed an independent binding SCFA at distinct modules. Altogether, could identify or predict over half Cache-type chemotactic selected commensals, carboxylic representing largest ligands. Among those, most commonly found were lactate formate, indicating particular importance these microbiome consistent observed beneficial impact growth bacterial species.

Language: Английский

Citations

1
Framework for exploring the sensory repertoire of the human gut microbiota DOI Creative Commons

Patricia A. Ross,

Wenhao Xu, Ekaterina Jalomo-Khayrova

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(6)

Published: May 17, 2024

ABSTRACT Bacteria sense changes in their environment and transduce signals to adjust cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial is studied mainly a few model organisms, but advances genome sequencing analysis offer new ways of exploring the sensory repertoire many understudied organisms. The human gut natural target line study: it nutrient-rich dynamic home thousands species whose activities impact health. Many commensals are also poorly compared organisms known through sequences. To begin respond to, we have designed framework that enables identification domains, prediction they recognize, experimental verification these predictions. We validate framework’s functionality systematically identifying amino acid selected genomes metagenomes, characterizing binding properties, demonstrating potential. IMPORTANCE central process governing how environment. complex with living fluctuating streams nutrients. One inhabitant, Escherichia coli , organism for studying transduction. However, E. not representative most microbes, signaling pathways other comprising microbiota remain understood. This work provides foundation explore recognized

Language: Английский

Citations

5
Functional characterization of the methyl-accepting chemotaxis proteins RS10830 and RS10815 in Xanthomonas oryzae pv. oryzicola DOI
J. P. Liu, Yuxin Wang,

Yuying Zhou

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 306, P. 141800 - 141800

Published: March 5, 2025

Language: Английский

Citations

0
Structural and functional diversity of sensor domains in bacterial transmembrane receptors DOI
Miguel A. Matilla, J.A. Gavira, Elizabet Monteagudo‐Cascales

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Bacterial amino acid chemotaxis: a widespread strategy with multiple physiological and ecological roles DOI
Miguel A. Matilla, Tino Krell

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

ABSTRACT Chemotaxis is the directed, flagellum-based movement of bacteria in chemoeffector gradients. Bacteria respond chemotactically to a wide range chemoeffectors, including amino, organic, and fatty acids, sugars, polyamines, quaternary amines, purines, pyrimidines, aromatic hydrocarbons, oxygen, inorganic ions, or polysaccharides. Most frequent are chemotactic responses amino acids (AAs), which were observed numerous regardless their phylogeny lifestyle. Mostly chemoattraction observed, although number repelled from certain AAs. Chemoattraction associated with important metabolic value AAs as growth substrates building blocks proteins. However, additional studies revealed that also sensed environmental cues. Many chemoreceptors specific for AAs, signaling typically initiated by direct ligand binding four-helix bundle dCache ligand-binding domains. Frequently, possess multiple AA-responsive at times complementary AA spectra. The identification sequence motifs sites dCache_1 domains has permitted define an AA-specific family dCache_1AA chemoreceptors. In addition, among ligands recognized broad chemoreceptors, evidence was obtained chemoreceptor activation AA-loaded solute-binding biological significance chemotaxis very ample biofilm formation, root seed colonization beneficial bacteria, plant entry phytopathogens, intestine, different virulence-related features human/animal pathogens. This review provides insights may be helpful study other uncharacterized bacteria.

Language: Английский

Citations

1
Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria DOI Open Access
Elizabet Monteagudo‐Cascales, Vadim M. Gumerov, Matilde Fernández

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 26, 2023

Abstract Purines and their derivatives are key molecules for controlling intracellular energy homeostasis nucleotide synthesis. In eukaryotes, including humans, purines also act as signaling that mediate extracellular communication control cellular processes, such proliferation, migration, differentiation, apoptosis. However, the role of in bacteria is largely unknown. Here, by combining structural sequence information, we define a purine-binding motif, which present sensor domains thousands bacterial receptors modulate motility, gene expression, metabolism second messenger turnover. The screening compound libraries microcalorimetric titrations selected validated ability to specifically bind purine derivatives. physiological relevance sensing was demonstrated system modulates c-di-GMP levels.

Language: Английский

Citations

2
The chemoreceptor controlling the Wsp-like transduction pathway in Halomonas titanicae KHS3 binds purine derivatives DOI Creative Commons

Fernando E. Ramos Ricciuti,

M. Karina Herrera Seitz, Ana Gasperotti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 9, 2024

Abstract The chemosensory pathway Ht Che2 from the marine bacterium Halomonas titanicae KHS3 controls activity of a diguanylate cyclase. Constitutive activation results in colony morphology alterations and increased ability to form biofilm. Such characteristics resemble behaviour Wsp Pseudomonas . In this work we investigate specificity Htc10, only chemoreceptor coded within gene cluster. Thermal shift analyses performed with Htc10 ligand-binding domain led identification purine derivatives as ligands. This was crystallized presence guanine or hypoxanthine its structure solved by X-ray protein crystallography. sensor adopts double-cache folding, ligands bound membrane-distal pocket. A high-resolution occupied guanine-binding pocket allowed involved residues. These residues were validated site directed mutagenesis thermal isothermal calorimetry variants. dissociation constants for intact low micromolar range. To our knowledge, is first description binding that an associated cyclase, opens way dynamic studies signalling kind sensory complex. comparison between functionally equivalent WspA receptor revealed no significant sequence similarities. contrast, highly conserved Htc10-like receptors found distant bacteria carrying Che2-like clusters.

Language: Английский

Citations

0