Royer, A.L.M., Umansky, A.A., Allen, M.-M. et al. (7 more authors) (2023) Clostridioides difficile S-layer protein A (SlpA) serves as a general phage receptor. Microbiology Spectrum, 11 (2). e03894-22. ISSN 2165-0497
Abstract
Therapeutic bacteriophages (phages) are being considered as alternatives in the fight against Clostridioides difficile infections. To be efficient, phages should have a wide host range, buthe lack of knowledge about the cell receptor used by C. difficile phages hampers the rational design of phage cocktails. Recent reports suggested that the C. difficile surface layer protein A (SlpA) is an important phage receptor, but available data are still limited. Here, using the epidemic R20291 strain and its FM2.5 mutant derivative lacking a functional S-layer, we show that the absence of SlpA renders cells completely resistant to infection by ϕCD38-2, ϕCD111, and ϕCD146, which normally infect the parental strain. Complementation with 12 different S-layer cassette types (SLCTs) expressed from a plasmid revealed that SLCT-6 also allowed infection by ϕCD111 and SLCT-11 enabled infection by ϕCD38-2 and ϕCD146. Of note, the expression of SLCT-1, -6, -8, -9, -10, or -12 conferred susceptibility to infection by 5 myophages that normally do not infect the R20291 strain. Also, deletion of the D2 domain within the low-molecular-weight fragment of SlpA was found to abolish infection by ϕCD38-2 and ϕCD146 but not ϕCD111. Altogether, our data suggest that many phages use SlpA as their receptor and, most importantly, that both siphophages and myophages target SlpA despite major differences in their tail structures. Our study therefore represents an important step in understanding the interactions between C. difficile and its phages.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 Royer et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license. (https://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Feb 2023 10:02 |
Last Modified: | 27 Sep 2024 15:16 |
Status: | Published |
Publisher: | American Society for Microbiology |
Refereed: | Yes |
Identification Number: | 10.1128/spectrum.03894-22 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:196455 |