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Open AccessArticle

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

1
PhagoMed Biopharma GmbH, Vienna Biocenter, 1110 Wien, Austria
2
Laboratory Bacteriology Research, Department of Diagnostic Sciences, Faculty of Medicine & Health Sciences, Ghent University, Flanders, 9000 Gent, Belgium
3
Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, 51-148 Wroclaw, Poland
4
Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology Moscow, 119071 Moscow, Russia
5
Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland
6
MDI Limbach Berlin GmbH, 13407 Berlin, Germany
7
Medizinische Klinik, Charité CCM, Humboldt Universität, 10117 Berlin, Germany
8
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
*
Author to whom correspondence should be addressed.
Pathogens 2021, 10(1), 54; https://doi.org/10.3390/pathogens10010054
Received: 8 December 2020 / Revised: 31 December 2020 / Accepted: 5 January 2021 / Published: 8 January 2021
(This article belongs to the Section Human Pathogens)
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. View Full-Text
Keywords: bacterial vaginosis; Gardnerella biofilm; prophage; endolysin; genus-specificity; antimicrobial resistance; alternative to antibiotic treatment bacterial vaginosis; Gardnerella biofilm; prophage; endolysin; genus-specificity; antimicrobial resistance; alternative to antibiotic treatment
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MDPI and ACS Style

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. Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo. Pathogens 2021, 10, 54. https://doi.org/10.3390/pathogens10010054

AMA Style

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. Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo. Pathogens. 2021; 10(1):54. https://doi.org/10.3390/pathogens10010054

Chicago/Turabian Style

Landlinger, Christine; Tisakova, Lenka; Oberbauer, Vera; Schwebs, Timo; Muhammad, Abbas; Latka, Agnieszka; Van Simaey, Leen; Vaneechoutte, Mario; Guschin, Alexander; Resch, Gregory; Swidsinski, Sonja; Swidsinski, Alexander; Corsini, Lorenzo. 2021. "Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo" Pathogens 10, no. 1: 54. https://doi.org/10.3390/pathogens10010054

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