Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium

Vizarraga, D; Kawamoto, A; Marcos-Silva, M; Martín, J; Makino, F; Miyata, T; Roel-Touris, J; Marcos, E; Pich, OQ; Aparicio, D; Fita, I; Miyata, M; Piñol, J; Namba, K; Kenri, T

Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium

Mycoplasma pneumoniae and Mycoplasma genitalium are bacterial wall-less human pathogens and the causative agents of respiratory and reproductive tract infections. Infectivity, gliding motility and adhesion of these mycoplasmas to host cells are mediated by orthologous adhesin proteins forming a tran...

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Autores:	Vizarraga, D, Kawamoto, A, Marcos-Silva, M, Martín, J, Makino, F, Miyata, T, Roel-Touris, J, Marcos, E, Pich, OQ, Aparicio, D, Fita, I, Miyata, M, Piñol, J, Namba, K, Kenri, T
Tipo de documento:	artigo
Estado:	Versão publicada
Data de publicação:	2025
País:	España
Recursos:	Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositório:	r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:	oai:i3pt.fundanetsuite.com:p6312
Acesso em linha:	https://i3pt.portalinvestigacion.com/publicaciones/6312 https://www.scopus.com/inward/record.uri?eid=2-s2.0-105001655101&doi=10.1371%2Fjournal.ppat.1012973&partnerID=40&md5=eea9e7e6c87994dcff8907a60e7a4867
Access Level:	Acceso aberto
Palavra-chave:	epitope monoclonal antibody oligosaccharide adhesin Article cell adhesion cell invasion controlled study crystal structure dynamics Escherichia coli flow cytometry genital tract infection human human cell immunofluorescence microscopy light scattering mouse Mycoplasma genitalium Mycoplasma genitalium infection Mycoplasma pneumoniae nonhuman pathogenesis polyacrylamide gel electrophoresis Sanger sequencing scanning electron microscopy size exclusion chromatography Western blotting bacterium adherence chemistry cryoelectron microscopy genetics immunology metabolism microbiology Mycoplasma infection physiology Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma Infections

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spelling	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitaliumVizarraga, DKawamoto, AMarcos-Silva, MMartín, JMakino, FMiyata, TRoel-Touris, JMarcos, EPich, OQAparicio, DFita, IMiyata, MPiñol, JNamba, KKenri, Tepitopemonoclonal antibodyoligosaccharideadhesinArticlecell adhesioncell invasioncontrolled studycrystal structuredynamicsEscherichia coliflow cytometrygenital tract infectionhumanhuman cellimmunofluorescence microscopylight scatteringmouseMycoplasma genitaliumMycoplasma genitalium infectionMycoplasma pneumoniaenonhumanpathogenesispolyacrylamide gel electrophoresisSanger sequencingscanning electron microscopysize exclusion chromatographyWestern blottingbacterium adherencechemistrycryoelectron microscopygeneticsimmunologymetabolismmicrobiologyMycoplasma infectionphysiologyAdhesins, BacterialBacterial AdhesionCryoelectron MicroscopyHumansMycoplasma InfectionsMycoplasma pneumoniae and Mycoplasma genitalium are bacterial wall-less human pathogens and the causative agents of respiratory and reproductive tract infections. Infectivity, gliding motility and adhesion of these mycoplasmas to host cells are mediated by orthologous adhesin proteins forming a transmembrane adhesion complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of M. pneumoniae P1 adhesin bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motile cells. The epitope of P1/MCA4 involves residues only from the small C-domain of P1. This epitope is accessible to antibodies only in the "closed conformation" of the adhesion complex and is not accessible in the "open" conformation, when the adhesion complex is ready for attachment to sialylated oligosaccharides. Polyclonal antibodies generated against the large N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. Moreover, mutations in the highly conserved Engelman motifs found in the transmembrane helix of M. genitalium P110 adhesin also alter adhesion and motility. These results show that antibodies directed to the C-domain of P1 hinder the large conformational rearrangements in this domain required to alternate between the "open" and "closed" conformations of the adhesion complex. Since transition between both conformations is essential to complete the attachment/detachment cycle of the adhesion complex, interfering with the gliding of mycoplasma cells and providing a new potential target to confront M. pneumoniae and M. genitalium infections.PUBLIC LIBRARY SCIENCE2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/6312https://www.scopus.com/inward/record.uri?eid=2-s2.0-105001655101&doi=10.1371%2Fjournal.ppat.1012973&partnerID=40&md5=eea9e7e6c87994dcff8907a60e7a4867PLoS PathogensISSN: 15537366ISSNe: 15537374reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:i3pt.fundanetsuite.com:p63122026-06-21T15:30:37Z
dc.title.none.fl_str_mv	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
title	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
spellingShingle	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium Vizarraga, D epitope monoclonal antibody oligosaccharide adhesin Article cell adhesion cell invasion controlled study crystal structure dynamics Escherichia coli flow cytometry genital tract infection human human cell immunofluorescence microscopy light scattering mouse Mycoplasma genitalium Mycoplasma genitalium infection Mycoplasma pneumoniae nonhuman pathogenesis polyacrylamide gel electrophoresis Sanger sequencing scanning electron microscopy size exclusion chromatography Western blotting bacterium adherence chemistry cryoelectron microscopy genetics immunology metabolism microbiology Mycoplasma infection physiology Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma Infections
title_short	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
title_full	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
title_fullStr	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
title_full_unstemmed	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
title_sort	Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium
dc.creator.none.fl_str_mv	Vizarraga, D Kawamoto, A Marcos-Silva, M Martín, J Makino, F Miyata, T Roel-Touris, J Marcos, E Pich, OQ Aparicio, D Fita, I Miyata, M Piñol, J Namba, K Kenri, T
author	Vizarraga, D
author_facet	Vizarraga, D Kawamoto, A Marcos-Silva, M Martín, J Makino, F Miyata, T Roel-Touris, J Marcos, E Pich, OQ Aparicio, D Fita, I Miyata, M Piñol, J Namba, K Kenri, T
author_role	author
author2	Kawamoto, A Marcos-Silva, M Martín, J Makino, F Miyata, T Roel-Touris, J Marcos, E Pich, OQ Aparicio, D Fita, I Miyata, M Piñol, J Namba, K Kenri, T
author2_role	author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	epitope monoclonal antibody oligosaccharide adhesin Article cell adhesion cell invasion controlled study crystal structure dynamics Escherichia coli flow cytometry genital tract infection human human cell immunofluorescence microscopy light scattering mouse Mycoplasma genitalium Mycoplasma genitalium infection Mycoplasma pneumoniae nonhuman pathogenesis polyacrylamide gel electrophoresis Sanger sequencing scanning electron microscopy size exclusion chromatography Western blotting bacterium adherence chemistry cryoelectron microscopy genetics immunology metabolism microbiology Mycoplasma infection physiology Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma Infections
topic	epitope monoclonal antibody oligosaccharide adhesin Article cell adhesion cell invasion controlled study crystal structure dynamics Escherichia coli flow cytometry genital tract infection human human cell immunofluorescence microscopy light scattering mouse Mycoplasma genitalium Mycoplasma genitalium infection Mycoplasma pneumoniae nonhuman pathogenesis polyacrylamide gel electrophoresis Sanger sequencing scanning electron microscopy size exclusion chromatography Western blotting bacterium adherence chemistry cryoelectron microscopy genetics immunology metabolism microbiology Mycoplasma infection physiology Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma Infections
description	Mycoplasma pneumoniae and Mycoplasma genitalium are bacterial wall-less human pathogens and the causative agents of respiratory and reproductive tract infections. Infectivity, gliding motility and adhesion of these mycoplasmas to host cells are mediated by orthologous adhesin proteins forming a transmembrane adhesion complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of M. pneumoniae P1 adhesin bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motile cells. The epitope of P1/MCA4 involves residues only from the small C-domain of P1. This epitope is accessible to antibodies only in the "closed conformation" of the adhesion complex and is not accessible in the "open" conformation, when the adhesion complex is ready for attachment to sialylated oligosaccharides. Polyclonal antibodies generated against the large N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. Moreover, mutations in the highly conserved Engelman motifs found in the transmembrane helix of M. genitalium P110 adhesin also alter adhesion and motility. These results show that antibodies directed to the C-domain of P1 hinder the large conformational rearrangements in this domain required to alternate between the "open" and "closed" conformations of the adhesion complex. Since transition between both conformations is essential to complete the attachment/detachment cycle of the adhesion complex, interfering with the gliding of mycoplasma cells and providing a new potential target to confront M. pneumoniae and M. genitalium infections.
publishDate	2025
dc.date.none.fl_str_mv	2025
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://i3pt.portalinvestigacion.com/publicaciones/6312 https://www.scopus.com/inward/record.uri?eid=2-s2.0-105001655101&doi=10.1371%2Fjournal.ppat.1012973&partnerID=40&md5=eea9e7e6c87994dcff8907a60e7a4867
url	https://i3pt.portalinvestigacion.com/publicaciones/6312 https://www.scopus.com/inward/record.uri?eid=2-s2.0-105001655101&doi=10.1371%2Fjournal.ppat.1012973&partnerID=40&md5=eea9e7e6c87994dcff8907a60e7a4867
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	PUBLIC LIBRARY SCIENCE
publisher.none.fl_str_mv	PUBLIC LIBRARY SCIENCE
dc.source.none.fl_str_mv	PLoS Pathogens ISSN: 15537366 ISSNe: 15537374 reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str	Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str	r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection	r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitalium

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