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

<b>Background/Objectives:</b> Nisin A, an antimicrobial peptide produced by <i>Lactococcus lactis</i>, 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 <i>Candida</i>, occurs in immunocompromised patients and requires antifungal therapy. However, antifungal drug-resistant <i>Candida</i> strains are increasing worldwide, leading to serious problems. <b>Methods:</b> To examine the effects of nisin A against <i>Candida</i> species, we investigated the combined effects of nisin A and antifungal drugs on the growth and viability of <i>Candida</i> strains. <b>Results:</b> While nisin A alone had no antifungal effect, together with amphotericin (AMPH), it showed synergistic effects towards <i>C. albicans</i>, as well as the non-albican strains <i>C. glabrata</i>, <i>C tropicalis</i>, and <i>C. parapsilosis</i> 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 <i>C. albicans</i> and <i>C. glabrata</i>. Biofilm reduction assays showed that nisin A with AMPH, MCZ, or MCFG inhibited biofilm activity against <i>C. albicans</i> 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 <i>C. albicans</i> and <i>C. glabrata.</i><b>Conclusions:</b> 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 <i>Candida</i> species.