Exploring the antibacterial potential of a designed peptide against Gardnerella vaginalis

Bacterial vaginosis (BV) is a common vaginal dysbiosis caused by Gardnerella vaginalis, a facultative anaerobic bacillus. The failure of conventional antibiotics and recurrence of bacterial vaginosis call for alternative novel therapeutic strategies. Antimicrobial peptides (AMPs) provide a targeted, resistance-sparing alternative with their broad-spectrum activity and distinct mode of action.

Two AMPs, i.e., TCCP-1 (cyclic) and ZMLP-2 (linear), were designed in silico from proteome sequences of Thymbra capitata and Zataria multiflora already available in NCBI. The designed peptides were chemically synthesized, evaluated for their antibacterial activity, cytotoxicity, hemolytic effects and mechanism of action against G.vaginalis.

TCCP-1, a cyclic peptide with an MIC of 1.95 µg/mL against G. vaginalis showed minimal cytotoxicity even at 100 µg/mL, which is much higher than its MIC value (1.95 µg/mL). TCCP-1 maintained high cell viability at lower concentrations, while a concentration-dependent reduction in viability was observed at higher concentrations. In contrast, ZMLP-2, a linear AMP, showed weak antimicrobial activity with an MIC of 100 µg/mL, exhibited a moderate reduction in cell viability (~ 70-75%) when tested at 100 µg/mL or a concentration below its MIC. Both peptides showed the disruption of bacterial membranes and, therefore, support the re-establishment of healthy vaginal flora. More significantly, TCCP-1 demonstrated efficient antimicrobial activity against G.vaginalis along with decreased cytotoxicity, making it an excellent candidate for future in vivo studies and possible clinical uses.

Thus, plant-derived AMPs could prove to be useful, targeted, and sustainable alternatives to BV prevention while treating both resistance and recurrence.