In vitro bacterial vaginosis biofilm community manipulation using endolysin therapy

Johnston, W., Ware, A., Kuiters, W. F., Delaney, C., Brown, J. L. , Hagen, S., Corcoran, D., Cummings, M., Ramage, G. and Kean, R. (2023) In vitro bacterial vaginosis biofilm community manipulation using endolysin therapy. Biofilm, 5, 100101. (doi: 10.1016/j.bioflm.2022.100101) (PMID:36655001) (PMCID:PMC9841237)

Abstract

Bacterial vaginosis (BV) affects approximately 26% of women of childbearing age globally, presenting with 3–5 times increased risk of miscarriage and two-fold risk of pre-term birth. Antibiotics (metronidazole and clindamycin) are typically employed to treat BV; however the success rate is low due to the formation of recalcitrant polymicrobial biofilms. As a novel therapeutic, promising results have been obtained in vitro using Gardnerella endolysins, although to date their efficacy has only been demonstrated against simple biofilm models. In this study, a four-species biofilm was developed consisting of Gardnerella vaginalis, Fannyhessea vaginae, Prevotella bivia and Mobiluncus curtisii. Biofilms were grown in NYC III broth and treated using antibiotics and an anti-Gardnerella endolysin (CCB7.1) for 24 h. Biofilm composition, viability and structure were assessed using colony counts, live/dead qPCR and scanning electron microscopy. All species colonised biofilms to varying degrees, with G. vaginalis being the most abundant. Biofilm composition remained largely unchanged when challenged with escalated concentrations of conventional antibiotics. A Gardnerella-targeted endolysin candidate (CCB7.1) showed efficacy against several Gardnerella species planktonically, and significantly reduced viable G. vaginalis within polymicrobial biofilms at 1 to 4X pMIC (p < 0.05 vs. vehicle control). Collectively, this study highlights the resilience of biofilm-embedded pathogens against the currently used antibiotics and provides a polymicrobial model that allows for more effective pre-clinical screening of BV therapies. The Gardnerella-specific endolysin CCB7.1 demonstrated significant activity against G. vaginalis within polymicrobial biofilms, altering the overall community dynamic and composition.

• Item Type: Articles
• Additional Information: The current study was supported by the National Biofilms Innovation Centre (NBIC) under project number: 04POC21-235 and an Innovation Seed Funding award from Scottish Universities Life Sciences Alliance.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kean, Mr Ryan and Ramage, Professor Gordon and Brown, Dr Jason and Delaney, Mr Christopher
• Authors: Johnston, W., Ware, A., Kuiters, W. F., Delaney, C., Brown, J. L., Hagen, S., Corcoran, D., Cummings, M., Ramage, G., and Kean, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Biofilm
• Publisher: Elsevier
• ISSN: 2590-2075
• ISSN (Online): 2590-2075
• Published Online: 29 December 2022
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Biofilm 5: 100101
• Publisher Policy: Reproduced under a Creative Commons License