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...
| Autores: | , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:319543 |
| Acceso en línea: | https://ddd.uab.cat/record/319543 https://dx.doi.org/urn:doi:10.1371/journal.ppat.1012973 |
| Access Level: | acceso abierto |
| Palabra clave: | Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma genitalium Mycoplasma Infections Mycoplasma pneumoniae |
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Dynamics of the adhesion complex of the human pathogens Mycoplasma pneumoniae and Mycoplasma genitaliumVizarraga, D.Kawamoto, A.Marcos-Silva, M.Martín i Pedret, Joaquim|||0000-0002-7467-787XMakino, F.Miyata, T.Roel-Touris, J.Marcos, E.Quijada Pich, Oscar|||0000-0003-3561-630XAparicio, D.Fita, I.Miyata, M.Piñol Ribas, Jaume|||0000-0002-9055-8934Namba, K.Kenri, Tsuyoshi|||0000-0002-3198-4263Adhesins, BacterialBacterial AdhesionCryoelectron MicroscopyHumansMycoplasma genitaliumMycoplasma InfectionsMycoplasma pneumoniaeMycoplasma 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. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/319543https://dx.doi.org/urn:doi:10.1371/journal.ppat.1012973reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3195432026-06-06T12:50:31Z |
| 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. Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma genitalium Mycoplasma Infections Mycoplasma pneumoniae |
| 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 i Pedret, Joaquim|||0000-0002-7467-787X Makino, F. Miyata, T. Roel-Touris, J. Marcos, E. Quijada Pich, Oscar|||0000-0003-3561-630X Aparicio, D. Fita, I. Miyata, M. Piñol Ribas, Jaume|||0000-0002-9055-8934 Namba, K. Kenri, Tsuyoshi|||0000-0002-3198-4263 |
| author |
Vizarraga, D. |
| author_facet |
Vizarraga, D. Kawamoto, A. Marcos-Silva, M. Martín i Pedret, Joaquim|||0000-0002-7467-787X Makino, F. Miyata, T. Roel-Touris, J. Marcos, E. Quijada Pich, Oscar|||0000-0003-3561-630X Aparicio, D. Fita, I. Miyata, M. Piñol Ribas, Jaume|||0000-0002-9055-8934 Namba, K. Kenri, Tsuyoshi|||0000-0002-3198-4263 |
| author_role |
author |
| author2 |
Kawamoto, A. Marcos-Silva, M. Martín i Pedret, Joaquim|||0000-0002-7467-787X Makino, F. Miyata, T. Roel-Touris, J. Marcos, E. Quijada Pich, Oscar|||0000-0003-3561-630X Aparicio, D. Fita, I. Miyata, M. Piñol Ribas, Jaume|||0000-0002-9055-8934 Namba, K. Kenri, Tsuyoshi|||0000-0002-3198-4263 |
| author2_role |
author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma genitalium Mycoplasma Infections Mycoplasma pneumoniae |
| topic |
Adhesins, Bacterial Bacterial Adhesion Cryoelectron Microscopy Humans Mycoplasma genitalium Mycoplasma Infections Mycoplasma pneumoniae |
| 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 |
2 2025-01-01 2025 2025-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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info:eu-repo/semantics/article |
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article |
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https://ddd.uab.cat/record/319543 https://dx.doi.org/urn:doi:10.1371/journal.ppat.1012973 |
| url |
https://ddd.uab.cat/record/319543 https://dx.doi.org/urn:doi:10.1371/journal.ppat.1012973 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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