An internal thioester in a pathogen surface protein mediates covalent host binding

Miriam Walden; John Michael Edwards; Aleksandra Malgorzata Dziewulska; Rene Bergmann; Gerhard Saalbach; Su-Yin Kan; Ona Kealoha Miller; Miriam Weckener; Rosemary J. Jackson; Sally Lorna Shirran; Catherine Helen Botting; Gordon John Florence; Manfred Rohde; Mark J. Banfield; Uli Schwarz-Linek

doi:10.7554/eLife.06638

An internal thioester in a pathogen surface protein mediates covalent host binding

Miriam Walden, John Michael Edwards, Aleksandra Malgorzata Dziewulska, Rene Bergmann, Gerhard Saalbach, Su-Yin Kan, Ona Kealoha Miller, Miriam Weckener, Rosemary J. Jackson, Sally Lorna Shirran, Catherine Helen Botting, Gordon John Florence, Manfred Rohde, Mark J. Banfield, Uli Schwarz-Linek

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e06638
Number of pages	24
Journal	eLife
Volume	4
DOIs	https://doi.org/10.7554/eLife.06638
Publication status	Published - 2 Jun 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Streptococcus pyogenes
Streptococcus pneumoniae
Clostridium perfringens
Host-microbe interactions
Fibrinogen
Bacterial surface proteins

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10.7554/eLife.06638Licence: CC BY

e06638.full
Copyright © 2015, Walden et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Final published version, 4.07 MBLicence: CC BY

Cite this

Walden, M., Edwards, J. M., Dziewulska, A. M., Bergmann, R., Saalbach, G., Kan, S.-Y., Miller, O. K., Weckener, M., Jackson, R. J., Shirran, S. L., Botting, C. H., Florence, G. J., Rohde, M., Banfield, M. J., & Schwarz-Linek, U. (2015). An internal thioester in a pathogen surface protein mediates covalent host binding. eLife, 4, Article e06638. https://doi.org/10.7554/eLife.06638

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abstract = "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 {\textquoteleft}chemical harpoon{\textquoteright}. 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.",

keywords = "Streptococcus pyogenes, Streptococcus pneumoniae, Clostridium perfringens, Host-microbe interactions, Fibrinogen, Bacterial surface proteins",

author = "Miriam Walden and Edwards, \{John Michael\} and Dziewulska, \{Aleksandra Malgorzata\} and Rene Bergmann and Gerhard Saalbach and Su-Yin Kan and Miller, \{Ona Kealoha\} and Miriam Weckener and Jackson, \{Rosemary J.\} and Shirran, \{Sally Lorna\} and Botting, \{Catherine Helen\} and Florence, \{Gordon John\} and Manfred Rohde and Banfield, \{Mark J.\} and Uli Schwarz-Linek",

note = "This work was supported by the MRC, UK grant MR/K001485 for MW, JME, MR, MJB, USL; the BBSRC, UK grant BB/J00453 and the John Innes Foundation for MJB; the Wellcome Trust Institutional Strategic Support Fund 097831/Z/11/B for AMD; Wellcome Trust/JIF award 063597 and Wellcome Trust grants WT079272AIA and 094476/Z/10/Z to CHB for the BSRC Mass Spectrometry and Proteomics Facility; University of St Andrews and School of Biology for SYK; The Carnegie Trust for OKM.",

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AU - Walden, Miriam

AU - Edwards, John Michael

AU - Dziewulska, Aleksandra Malgorzata

AU - Bergmann, Rene

AU - Saalbach, Gerhard

AU - Kan, Su-Yin

AU - Miller, Ona Kealoha

AU - Weckener, Miriam

AU - Jackson, Rosemary J.

AU - Shirran, Sally Lorna

AU - Botting, Catherine Helen

AU - Florence, Gordon John

AU - Rohde, Manfred

AU - Banfield, Mark J.

AU - Schwarz-Linek, Uli

N1 - This work was supported by the MRC, UK grant MR/K001485 for MW, JME, MR, MJB, USL; the BBSRC, UK grant BB/J00453 and the John Innes Foundation for MJB; the Wellcome Trust Institutional Strategic Support Fund 097831/Z/11/B for AMD; Wellcome Trust/JIF award 063597 and Wellcome Trust grants WT079272AIA and 094476/Z/10/Z to CHB for the BSRC Mass Spectrometry and Proteomics Facility; University of St Andrews and School of Biology for SYK; The Carnegie Trust for OKM.

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Y1 - 2015/6/2

N2 - 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.

AB - 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.

KW - Streptococcus pyogenes

KW - Streptococcus pneumoniae

KW - Clostridium perfringens

KW - Host-microbe interactions

KW - Fibrinogen

KW - Bacterial surface proteins

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M3 - Article

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VL - 4

JO - eLife

JF - eLife

M1 - e06638

ER -

An internal thioester in a pathogen surface protein mediates covalent host binding

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Covalent host targeting: Covalent host targeting by thioester domains of Gram-positive pathogens

MaXis ESI QTOF mass spectrometer: Equipment only grant-Mass spectrometers for Proteomics, Lipidomics and focused Metabolomics research

Gordon Florence

Ulrich Schwarz-Linek