title: Natural antimicrobials subtilosin and lauramide arginine ethyl ester synergize with conventional antibiotics clindamycin and metronidazole against biofilms of Gardnerella vaginalis but not against biofilms of healthy vaginal lactobacilli.
abstract: The purpose of this study was to evaluate the ability of clindamycin and metronidazole to synergize with natural antimicrobials against biofilms of bacterial vaginosis (BV)-associated Gardnerella vaginalis. Minimum bactericidal concentrations for biofilm cells (MBCs-B) were determined for each antimicrobial. The MBCs-B of lauramide arginine ethyl ester (LAE), subtilosin, clindamycin and metronidazole were 50, 69.5, 20 and 500 μg mL(-1), respectively. A checkerboard assay and isobologram were used to analyze the type of interactions between these antimicrobials. The combination of metronidazole with natural antimicrobials did not inhibit planktonic lactobacilli. Clindamycin with either LAE or with subtilosin was inhibitory for planktonic but not for biofilm-associated lactobacilli. All tested antimicrobial combinations were inhibitory for BV-associated Mobiluncus curtisii and Peptostreptococcus anaerobius. LAE and subtilosin synergized with clindamycin and metronidazole against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli. The biofilms of BV-associated pathogens can be controlled by synergistically acting combinations of conventional antibiotics and natural antimicrobials which will help better management of current antibiotics, especially considering robust bacterial resistance. Our findings create a foundation for a new strategy in the effective control of vaginal infections.
authors.affiliation: Department of Biochemistry and Microbiology, Rutgers State University, New Brunswick, NJ 08901, USA Department of Microbiology, Veterinary College, Diyala University, Baqubah, Iraq.
authors.forename: Ammar
authors.initials: A
authors.lastname: Algburi
authors.affiliation: School of Arts and Science, Rutgers State University, New Brunswick, NJ 08901, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Volski
authors.affiliation: School of Environmental and Biological Sciences, Rutgers State University, New Brunswick, NJ 08901, USA tchikindas@aesop.rutgers.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Chikindas
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001430:Bacteriocins / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects; D002981:Clindamycin / Q000378:metabolism*; D004357:Drug Synergism; D004983:Ethanolamines / Q000378:metabolism*; D005260:Female; D006194:Gardnerella vaginalis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D008795:Metronidazole / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000378:metabolism*; D014621:Vagina / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D004983:Ethanolamines; D010456:Peptides, Cyclic; D008795:Metronidazole; D002981:Clindamycin; D001120:Arginine; C047828:sboA protein, Bacillus subtilis; C489258:arginine ethyl ester
keywords: Gardnerella vaginalis; antimicrobial synergy; biofilm; natural antimicrobials