Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine
Acetylcholine is a central biological signal molecule present in all kingdoms of life. In humans, acetylcholine is the primary neurotransmitter of the peripheral nervous system; it mediates signal transmission at neuromuscular junctions. Here, we show that the opportunistic human pathogen Pseudomona...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/275869 |
| Acceso en línea: | http://hdl.handle.net/10261/275869 |
| Access Level: | acceso abierto |
| Palabra clave: | Chemotaxis Chemoreceptor Pseudomonas aeruginosa Acetylcholine Pectobacterium atrosepticum Quaternary amines Neurotransmitter |
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| dc.title.none.fl_str_mv |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| title |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| spellingShingle |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine Matilla, Miguel A. Chemotaxis Chemoreceptor Pseudomonas aeruginosa Acetylcholine Pectobacterium atrosepticum Quaternary amines Neurotransmitter |
| title_short |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| title_full |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| title_fullStr |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| title_full_unstemmed |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| title_sort |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter Acetylcholine |
| dc.creator.none.fl_str_mv |
Matilla, Miguel A. Velando, Félix Tajuelo, Ana Martín-Mora, David Xu, Wenhao Sourjik, Victor Gavira Gallardo, J. A. Krell, Tino |
| author |
Matilla, Miguel A. |
| author_facet |
Matilla, Miguel A. Velando, Félix Tajuelo, Ana Martín-Mora, David Xu, Wenhao Sourjik, Victor Gavira Gallardo, J. A. Krell, Tino |
| author_role |
author |
| author2 |
Velando, Félix Tajuelo, Ana Martín-Mora, David Xu, Wenhao Sourjik, Victor Gavira Gallardo, J. A. Krell, Tino |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia e Innovación (España) Junta de Andalucía European Commission Hessen State Ministry of Higher Education, Research and the Arts European Synchrotron Radiation Facility ALBA Synchrotron Hessen State Ministry of Higher Education, Research and the Arts Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Chemotaxis Chemoreceptor Pseudomonas aeruginosa Acetylcholine Pectobacterium atrosepticum Quaternary amines Neurotransmitter |
| topic |
Chemotaxis Chemoreceptor Pseudomonas aeruginosa Acetylcholine Pectobacterium atrosepticum Quaternary amines Neurotransmitter |
| description |
Acetylcholine is a central biological signal molecule present in all kingdoms of life. In humans, acetylcholine is the primary neurotransmitter of the peripheral nervous system; it mediates signal transmission at neuromuscular junctions. Here, we show that the opportunistic human pathogen Pseudomonas aeruginosa exhibits chemoattraction toward acetylcholine over a concentration range of 1 mM to 100 mM. The maximal magnitude of the response was superior to that of many other P. aeruginosa chemoeffectors. We demonstrate that this chemoattraction is mediated by the PctD (PA4633) chemoreceptor. Using microcalorimetry, we show that the PctD ligand-binding domain (LBD) binds acetylcholine with a equilibrium dissociation constant (KD) of 23 mM. It also binds choline and with lower affinity betaine. Highly sensitive responses to acetylcholine and choline, and less sensitive responses to betaine and L-carnitine, were observed in Escherichia coli expressing a chimeric receptor comprising the PctD-LBD fused to the Tar chemoreceptor signaling domain. We also identified the PacA (ECA_RS10935) chemoreceptor of the phytopathogen Pectobacterium atrosepticum, which binds choline and betaine but fails to recognize acetylcholine. To identify the molecular determinants for acetylcholine recognition, we report high-resolution structures of PctD-LBD (with bound acetylcholine and choline) and PacA-LBD (with bound betaine). We identified an amino acid motif in PctD-LBD that interacts with the acetylcholine tail. This motif is absent in PacA-LBD. Significant acetylcholine chemotaxis was also detected in the plant pathogens Agrobacterium tumefaciens and Dickeya solani. To the best of our knowledge, this is the first report of acetylcholine chemotaxis and extends the range of host signals perceived by bacterial chemoreceptors. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2022 2022 |
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info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/275869 |
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http://hdl.handle.net/10261/275869 |
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Inglés |
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Inglés |
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#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-103972GA-I00 info:eu-repo/grantAgreement///PID2020-116261GB-I00 info:eu-repo/grantAgreement///PID2020-112612GB-I00 http://dx.doi.org/10.1128/mbio.03458-21 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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American Society for Microbiology |
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American Society for Microbiology |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869424989811245056 |
| spelling |
Chemotaxis of the human pathogen Pseudomonas aeruginosa to the neurotransmitter AcetylcholineMatilla, Miguel A.Velando, FélixTajuelo, AnaMartín-Mora, DavidXu, WenhaoSourjik, VictorGavira Gallardo, J. A.Krell, TinoChemotaxisChemoreceptorPseudomonas aeruginosaAcetylcholinePectobacterium atrosepticumQuaternary aminesNeurotransmitterAcetylcholine is a central biological signal molecule present in all kingdoms of life. In humans, acetylcholine is the primary neurotransmitter of the peripheral nervous system; it mediates signal transmission at neuromuscular junctions. Here, we show that the opportunistic human pathogen Pseudomonas aeruginosa exhibits chemoattraction toward acetylcholine over a concentration range of 1 mM to 100 mM. The maximal magnitude of the response was superior to that of many other P. aeruginosa chemoeffectors. We demonstrate that this chemoattraction is mediated by the PctD (PA4633) chemoreceptor. Using microcalorimetry, we show that the PctD ligand-binding domain (LBD) binds acetylcholine with a equilibrium dissociation constant (KD) of 23 mM. It also binds choline and with lower affinity betaine. Highly sensitive responses to acetylcholine and choline, and less sensitive responses to betaine and L-carnitine, were observed in Escherichia coli expressing a chimeric receptor comprising the PctD-LBD fused to the Tar chemoreceptor signaling domain. We also identified the PacA (ECA_RS10935) chemoreceptor of the phytopathogen Pectobacterium atrosepticum, which binds choline and betaine but fails to recognize acetylcholine. To identify the molecular determinants for acetylcholine recognition, we report high-resolution structures of PctD-LBD (with bound acetylcholine and choline) and PacA-LBD (with bound betaine). We identified an amino acid motif in PctD-LBD that interacts with the acetylcholine tail. This motif is absent in PacA-LBD. Significant acetylcholine chemotaxis was also detected in the plant pathogens Agrobacterium tumefaciens and Dickeya solani. To the best of our knowledge, this is the first report of acetylcholine chemotaxis and extends the range of host signals perceived by bacterial chemoreceptors.This work was supported by grants PID2019-103972GA-I00 (to M.A.M.), PID2020-116261GB-I00 (to J.A.G.) and PID2020-112612GB-I00 (to T.K.) from the Spanish Ministry for Science and Innovation/Agencia Estatal de Investigación 10.13039/501100011033, grant P18-FR-1621 (to T.K.) from the Junta de Andalucía, by the Hessian Ministry of Higher Education, Research, and the Arts (HMWK)–LOEWE research cluster “Diffusible Signals,” subproject A1 (to V.S.), and a Peterson Group “Serving Hometown” Elites scholarship to W.X. We thank Maria Rabyk for help with the hybrid receptor cloning. We are grateful to the European Synchrotron Radiation Facility (ESRF) for the provision of time through proposals MX2281 and MX2353 and to the staff at beamlines ID30B, ID23-1, and ID30A-3 and at the Xaloc beamline of the Alba Spanish synchrotron radiation source (Barcelona) for assistance during data collection.American Society for MicrobiologyMinisterio de Ciencia e Innovación (España)Junta de AndalucíaEuropean CommissionHessen State Ministry of Higher Education, Research and the ArtsEuropean Synchrotron Radiation FacilityALBA SynchrotronHessen State Ministry of Higher Education, Research and the ArtsConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/275869reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-103972GA-I00info:eu-repo/grantAgreement///PID2020-116261GB-I00info:eu-repo/grantAgreement///PID2020-112612GB-I00http://dx.doi.org/10.1128/mbio.03458-21Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2758692026-05-22T06:33:51Z |
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15,812429 |