Effects of Nisin A Combined with Antifungal Drug Against Growth of Candida Species.

Background/Objectives: Nisin A, an antimicrobial peptide produced by Lactococcus lactis, primarily shows antimicrobial activity against Gram-positive bacteria, with efficacy increased when used in combination with an antimicrobial drug. On the other hand, oral candidiasis, caused by Candida, occurs in immunocompromised patients and requires antifungal therapy. However, antifungal drug-resistant Candida strains are increasing worldwide, leading to serious problems. Methods: To examine the effects of nisin A against Candida species, we investigated the combined effects of nisin A and antifungal drugs on the growth and viability of Candida strains. Results: While nisin A alone had no antifungal effect, together with amphotericin (AMPH), it showed synergistic effects towards C. albicans, as well as the non-albican strains C. glabrata, C tropicalis, and C. parapsilosis in checkerboard assay results. Furthermore, nisin A with miconazole (MCZ) or micafungin (MCFG) demonstrated a synergistic or additive effect on those strains. Cell viability assay results showed that nisin A enhanced the fungicidal activity of AMPH against both C. albicans and C. glabrata. Biofilm reduction assays showed that nisin A with AMPH, MCZ, or MCFG inhibited biofilm activity against C. albicans as compared with each antifungal drug alone. Finally, nisin A with AMPH, MCZ, or MCFG resulted in a reduced minimum inhibitory concentration of those antifungal drugs against clinically isolated C. albicans and C. glabrata.Conclusions: When used in combination with nisin A, the antifungal drug dosage can be lowered, thus helping to prevent adverse side effects and the emergence of drug-resistant oral Candida species.