Gardnerella vaginalis contributes significantly to bacterial vaginosis, which causes an ecological imbalance in vaginal microbiota and presents with the depletion of Lactobacillus sp. Lactobacillus supplementation was reported to be an approach to treat bacterial vaginosis. We investigated the applicability of three Lactobacillus sp. strains (Lactobacillus delbrueckii DM8909, Lactiplantibacillus plantarum ATCC14917, and Lactiplantibacillus plantarum ZX27) based on their probiotic abilities in vitro. The three candidate Lactobacillus sp. strains for bacterial vaginosis therapy showed distinct properties in auto-aggregation ability, hydrophobicity, adhesion to cervical epithelial cells, and survivability in 0.01% hydrogen peroxide. Lpb. plantarum ZX27 showed a higher yield in producing short-chain fatty acids and lactic acid among the three candidate strains, and all three Lactobacillus sp. strains inhibited the growth and adhesion of G. vaginalis. Furthermore, we discovered that the culture supernatant of Lactobacillus sp. exhibited anti-biofilm activity against G. vaginalis. In particular, the Lpb. plantarum ZX27 supernatant treatment decreased the expression of genes related to virulence factors, adhesion, biofilm formation, metabolism, and antimicrobial resistance in biofilm-forming cells and suspended cells. Moreover, Lactobacillus sp. decreased the upregulated expression of interleukin−8 in HeLa cells induced by G. vaginalis or hydrogen peroxide. These results demonstrate the efficacy of Lactobacillus sp. application for treating bacterial vaginosis by limiting the growth, adhesion, biofilm formation, and virulence properties of G. vaginalis.

Emerging resistance to colistin in Acinetobacter baumannii is concerning because of the limited therapeutic options for this important clinical pathogen. Given the shortage of new antibiotics, one strategy that has been proven to be therapeutically effective is to overcome antibiotic-resistant pathogens by combining existing antibiotics with another antibiotic or non-antibiotic. This study was designed to investigate the potential synergistic antibacterial activity of amorolfine, a morpholine antifungal drug, in combination with colistin against A. baumannii. In this work, antibiotic susceptibility testing, checkerboard assays, and time-kill curves were used to investigate the synergistic efficacy of colistin combined with amorolfine. The molecular mechanisms of combination therapy were analyzed using fluorometric assays, UV-vis spectroscopy, and molecular docking. Finally, we evaluated the in vivo efficacy of combination therapy against A. baumannii. In brief, the combination therapy showed significant synergistic activity against A. baumannii (FICI = 0.094). In addition, the combination of amorolfine improved the membrane disruption of colistin, and amorolfine exhibited the capacity of binding to DNA. Moreover, in a mouse sepsis model, this combination therapy increased survival compared to colistin monotherapy. Our findings demonstrated that amorolfine serves as a potential colistin adjuvant against Acinetobacter baumannii.