The Natural Antimicrobial Peptide Subtilosin Acts Synergistically with Glycerol Monolaurate, Lauric Arginate, and ε-Poly- l -Lysine against Bacterial Vaginosis-Associated Pathogens but Not Human Lactobacilli

Abstract

bSubtilosin is a cyclical antimicrobial peptide produced by Bacillus amyloliquefaciens that has antimicrobial activity against the bacterial vaginosis-associated human pathogen Gardnerella vaginalis. The ability of subtilosin to inhibit G. vaginalis alone and in combination with the natural antimicrobial agents glycerol monolaurate (Lauricidin), lauric arginate, and -poly-L-lysine was tested using a checkerboard approach. Subtilosin was found to act synergistically with all of the chosen antimicrobials. These promising results indicate that lower concentrations of subtilosin in combination with other compounds could effectively be used to inhibit growth of the pathogen, thereby decreasing the risk of developed antimicrobial resistance. This is the first report on the effects of subtilosin combined with other natural antimicrobials against G. vaginalis.

Antibacterial Synergy of Glycerol Monolaurate and Aminoglycosides in Staphylococcus aureus Biofilms

“…This result is noteworthy considering that 0.35 mM GML is equivalent to 100 g/ml, and in other studies involving planktonic cells, the MIC of GML was reported to be Ն10 g/ml (3,4,25). Synergistic activity of GML with coenzyme Q1 (26) and lauric arginate (18) has been reported. Thus, using GML in combination with other agents may help combat biofilm drug resistance.…”

“…2C and D), indicating that GML might facilitate drug inter-action with matrix-embedded bacteria. There is evidence that signal transduction plays a role in GML-mediated inhibition of S. aureus virulence factors, such as beta-lactamase, alpha-hemolysin, and toxic shock syndrome toxin 1 (TSST-1), likely through inhibition of activity at microbial membranes (17)(18)(19). Because we have visual evidence that lipid may be a component of the matrix of S. aureus biofilms (20), it is plausible that GML's role as a surfactant might facilitate matrix penetration, and there is evidence that rhamnolipids and plant biosurfactants have antibiofilm effects (21).…”

Polyethylene Glycol-Based Hydrogels for Controlled Release of the Antimicrobial Subtilosin for Prophylaxis of Bacterial Vaginosis

“…The vaginal pathogen (10 8 CFU/ml) was added to the wells (200 l/well) and incubated anaerobically at 37°C for 48 h. Medium alone was used as the positive control and CLI (100 g/ml) as the negative control for growth. Following the incubation period, growth was evaluated by performing viable cell counts using the drop plate method (34,48). Cells were mechanically separated from the hydrogels by making a slit in the hydrogels using a pipette tip.…”

“…Recently, bacteriocins have been suggested as potential alternatives to antibiotics for the treatment of BV (31)(32)(33)(34)(35)(36). Unlike broad-spectrum antibiotics, some bacteriocins selectively target pathogenic microorganisms without disturbing the healthy vaginal flora.…”

“…Unlike broad-spectrum antibiotics, some bacteriocins selectively target pathogenic microorganisms without disturbing the healthy vaginal flora. One such bacteriocin, subtilosin A (referred to here as subtilosin), has demonstrated antimicrobial activity against several BV-associated pathogens, including G. vaginalis (34,37,38). Subtilosin is a cyclic anionic peptide produced by Bacillus subtilis and Bacillus amyloliquifaciens (33,39,40).…”