Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo.

Details

Serval ID
serval:BIB_AA638C21B4B1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo.
Journal
Pathogens
Author(s)
Landlinger C., Tisakova L., Oberbauer V., Schwebs T., Muhammad A., Latka A., Van Simaey L., Vaneechoutte M., Guschin A., Resch G., Swidsinski S., Swidsinski A., Corsini L.
ISSN
2076-0817 (Print)
ISSN-L
2076-0817
Publication state
Published
Issued date
08/01/2021
Peer-reviewed
Oui
Volume
10
Number
1
Pages
E54
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13-8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.
Keywords
Gardnerella biofilm, alternative to antibiotic treatment, antimicrobial resistance, bacterial vaginosis, endolysin, genus-specificity, prophage
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2021 10:11
Last modification date
16/02/2021 7:26
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