An internal thioester in a pathogen surface protein mediates covalent host binding
To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/06638 |
| _version_ | 1797997531772223488 |
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| author | Miriam Walden John M Edwards Aleksandra M Dziewulska Rene Bergmann Gerhard Saalbach Su-Yin Kan Ona K Miller Miriam Weckener Rosemary J Jackson Sally L Shirran Catherine H Botting Gordon J Florence Manfred Rohde Mark J Banfield Ulrich Schwarz-Linek |
| author_facet | Miriam Walden John M Edwards Aleksandra M Dziewulska Rene Bergmann Gerhard Saalbach Su-Yin Kan Ona K Miller Miriam Weckener Rosemary J Jackson Sally L Shirran Catherine H Botting Gordon J Florence Manfred Rohde Mark J Banfield Ulrich Schwarz-Linek |
| author_sort | Miriam Walden |
| collection | DOAJ |
| description | To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions. |
| first_indexed | 2024-04-11T10:33:10Z |
| format | Article |
| id | doaj.art-0ac783f109244594ad7361157650fd3d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:33:10Z |
| publishDate | 2015-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0ac783f109244594ad7361157650fd3d2022-12-22T04:29:21ZengeLife Sciences Publications LtdeLife2050-084X2015-06-01410.7554/eLife.06638An internal thioester in a pathogen surface protein mediates covalent host bindingMiriam Walden0John M Edwards1Aleksandra M Dziewulska2Rene Bergmann3Gerhard Saalbach4Su-Yin Kan5Ona K Miller6Miriam Weckener7Rosemary J Jackson8Sally L Shirran9Catherine H Botting10Gordon J Florence11Manfred Rohde12Mark J Banfield13Ulrich Schwarz-Linek14Department of Biological Chemistry, John Innes Centre, Norwich, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomCentral Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment of Biological Chemistry, John Innes Centre, Norwich, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomCentral Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment of Biological Chemistry, John Innes Centre, Norwich, United KingdomBiomedical Sciences Research Complex, University of St Andrews, St Andrews, United KingdomTo cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions.https://elifesciences.org/articles/06638Streptococcus pyogenesStreptococcus pneumoniaeClostridium perfringenshost-microbe interactionfibrinogenbacterial surface protein |
| spellingShingle | Miriam Walden John M Edwards Aleksandra M Dziewulska Rene Bergmann Gerhard Saalbach Su-Yin Kan Ona K Miller Miriam Weckener Rosemary J Jackson Sally L Shirran Catherine H Botting Gordon J Florence Manfred Rohde Mark J Banfield Ulrich Schwarz-Linek An internal thioester in a pathogen surface protein mediates covalent host binding eLife Streptococcus pyogenes Streptococcus pneumoniae Clostridium perfringens host-microbe interaction fibrinogen bacterial surface protein |
| title | An internal thioester in a pathogen surface protein mediates covalent host binding |
| title_full | An internal thioester in a pathogen surface protein mediates covalent host binding |
| title_fullStr | An internal thioester in a pathogen surface protein mediates covalent host binding |
| title_full_unstemmed | An internal thioester in a pathogen surface protein mediates covalent host binding |
| title_short | An internal thioester in a pathogen surface protein mediates covalent host binding |
| title_sort | internal thioester in a pathogen surface protein mediates covalent host binding |
| topic | Streptococcus pyogenes Streptococcus pneumoniae Clostridium perfringens host-microbe interaction fibrinogen bacterial surface protein |
| url | https://elifesciences.org/articles/06638 |
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