College of Biological Science and Medical Engineering, Donghua University, 2999 Renmin Road, Shanghai, 201620, China.
College of Biological Science and Medical Engineering, Donghua University, 2999 Renmin Road, Shanghai, 201620, China.
Res Microbiol. 2024 Nov-Dec;175(8):104245. doi: 10.1016/j.resmic.2024.104245. Epub 2024 Sep 7.
Previous studies on BSC2 have shown that it enhances yeast cell resistance to AmB via antioxidation and induces multidrug resistance by contributing to biofilm formation. Herein, we found that BSC2 overexpression could reverse the sensitivity of pmp3Δ to AmB and help the tested strains restore the intracellular sodium/potassium balance under exposure to AmB. Meanwhile, overexpression of the chitin gene CHS2 could simulate BSC2 to reverse the sensitivity of pmp3Δ and nha1Δ to high salt or AmB. However, BSC2 overexpression in flo11Δ failed to induce AmB resistance, form biofilms, and affect cell wall biogenesis, while CHS2 overexpression compensated the resistance of flo11Δ to AmB. Additionally, BSC2 levels were positively correlated with maintaining cell membrane integrity under exposure to AmB, CAS, or a combination of both. BSC2 overexpression in nha1Δ exhibited a similar function of CHS2, which can compensate for the sensitivity of the mutant to high salt. Altogether, the results demonstrate for the first time that BSC2 may promote ion equilibrium by strengthening cell walls and inhibiting membrane damage in a FLO path-dependent manner, thus enhancing the resistance of yeast cells to AmB. This study also reveals the possible mechanism of antifungal drugs CAS and AmB combined to inhibit fungi.
先前关于 BSC2 的研究表明，它通过抗氧化作用增强酵母细胞对 AmB 的抗性，并通过促进生物膜形成来诱导多药耐药性。在这里，我们发现 BSC2 的过表达可以逆转 pmp3Δ 对 AmB 的敏感性，并帮助测试菌株在暴露于 AmB 时恢复细胞内钠/钾平衡。同时，几丁质基因 CHS2 的过表达可以模拟 BSC2 逆转 pmp3Δ 和 nha1Δ 对高盐或 AmB 的敏感性。然而，flo11Δ 中 BSC2 的过表达不能诱导 AmB 耐药性、形成生物膜以及影响细胞壁生物发生，而 CHS2 的过表达补偿了 flo11Δ 对 AmB 的耐药性。此外，BSC2 水平与暴露于 AmB、CAS 或两者组合下保持细胞膜完整性呈正相关。nha1Δ 中 BSC2 的过表达表现出与 CHS2 相似的功能，它可以补偿突变体对高盐的敏感性。总之，这些结果首次表明，BSC2 可能通过增强细胞壁和抑制膜损伤以 FLO 途径依赖性的方式促进离子平衡，从而增强酵母细胞对 AmB 的抗性。本研究还揭示了 CAS 和 AmB 联合抑制真菌的可能机制。
