Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/24071
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dc.contributor.authorArroyo-Moreno, S-
dc.contributor.authorCummings, M-
dc.contributor.authorCorcoran, DB-
dc.contributor.authorCoffey, A-
dc.contributor.authorMcCarthy, RR-
dc.date.accessioned2022-02-07T12:25:15Z-
dc.date.available2022-02-07T12:25:15Z-
dc.date.issued2022-04-19-
dc.identifier20-
dc.identifier.citationArroyo-Moreno, S., Cummings, M., Corcoran, D.B., Coffey, A. and McCarthy, R.R. (2022) 'Identification and characterization of novel endolysins targeting Gardnerella vaginalis biofilms to treat bacterial vaginosis', npj Biofilms and Microbiomes, 8, 20, pp. 1-12. doi: .en_US
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/24071-
dc.description.sponsorshipInnovate UK Smart Grant 37800; British Society for Antimicrobial Chemotherapy BSAC-2018-0095, FRAME, Young European Research University Network Mobility Award, NC3Rs PhD Studentship NC/V001582/1; BBSRC New Investigator Award BB/V007823/1; Academy of Medical Sciences; Wellcome Trust; Government Department of Business, Energy and Industrial Strategy; British Heart Foundation; Diabetes UK Springboard Award [SBF006\1040]en_US
dc.description.sponsorshipInnovate UK (Development of clinically translatable therapies for the treatment and prevention of bacterial vaginosis).-
dc.format.extent1 - 12-
dc.format.mediumElectronic-
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.rightsCopyright © The Author(s) 2022. Rights and permissions. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.rights.uriCopyright © The Author(s) 2022. Bacterial vaginosis (BV) is a recurrent dysbiosis that is frequently associated with preterm birth, increased risk for acquisition of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The overgrowth of a key pathobiont, Gardnerella vaginalis, as a recalcitrant biofilm is central to the development of this dysbiosis. Overgrowth of vaginal biofilms, seeded by initial G. vaginalis colonization, leads to recurrent symptomatic BV which is poorly resolved by classically used antibiotics. In this light, the use of bacteriophages and/or their proteins, represents a promising alternative. Here we identify 84 diverse anti-Gardnerella endolysins across 7 protein families. A subset of 36 endolysin candidates were refactored and overexpressed in an E. coli BL21 (DE3) system and 5 biochemically and structurally diverse endolysins were fully characterized. Each candidate endolysin showed good lytic activity against planktonic G. vaginalis ATCC14018, as well as G. vaginalis clinical isolates. These endolysin candidates were assayed in biofilm prevention and disruption assays, with biofilm disruption at low microgram concentrations (5 μg/ml) observed. In addition to clonal G. vaginalis biofilms, endolysin candidates could also successfully disrupt polyspecies biofilms. Importantly, none of our candidates showed lytic activity against commensal lactobacilli present in the vaginal microbiota such as L. crispatus, L. jensenii, L. gasseri, and L. iners or against Atopobium vaginae (currently classified as Fannyhessa vaginae). The potency and selectivity of these novel endolysins constitute a promising alternative treatment to combat BV, avoiding problems associated with antibiotic resistance, while retaining beneficial commensal bacteria in the vaginal flora. The diverse library of candidates reported here represents a strong repository of endolysins for further preclinical development.-
dc.titleIdentification and characterization of novel endolysins targeting Gardnerella vaginalis biofilms to treat bacterial vaginosisen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1038/s41522-022-00285-0-
dc.relation.isPartOfnpj Biofilms and Microbiomes-
pubs.publication-statusPublished-
pubs.volume8-
dc.identifier.eissn2055-5008-
Appears in Collections:Dept of Life Sciences Research Papers

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