Medical Mycology Research Center, Chiba University, Chuo-ku, Japan.
FEMS Yeast Res. 2011 Aug;11(5):398-407. doi: 10.1111/j.1567-1364.2011.00728.x. Epub 2011 Apr 26.
It is known that cell wall remodeling and the salvaging pathway act to compensate for an impaired or a damaged cell wall. Lately, it has been indicated that this mechanism is partly required for resistance to the glucan synthesis inhibitor echinocandin. While cell wall remodeling has been described in mutants of glucan or mannan synthesis, it has not yet been reported in a chitin synthesis mutant. Here, we describe a novel cell wall remodeling and salvaging pathway in chitin synthesis mutants, Δchs3A and Δchs3B, of the pathogenic yeast Candida glabrata. Electron microscopic analysis revealed a thickened mannoprotein layer in Δchs3A cells and a thickened chitin-glucan layer of Δchs3B cells, and it indicated the hypothesis that mannan synthase and chitin-glucan synthase indemnify Δchs3A and Δchs3B cells, respectively. The double-mutant CHS3A and MNN10, encoding α-1,6-mannosyltransferase, showed synergistic stress sensitization, and the Δchs3B strain showed supersensitivity to echinocandins. Hence, these findings support the above hypothesis of remodeling. Furthermore, unlike Δchs3A cells, Δchs3B cells showed supersensitivity to calcineurin inhibitor FK506 and Tor1p kinase inhibitor rapamycin, indicating that the Δchs3B strain uses the calcineurin pathway and a Tor1p kinase for cell wall remodeling.
已知细胞壁重塑和回收途径可用于补偿受损或受损的细胞壁。最近，有人指出，这种机制部分是对抗葡聚糖合成抑制剂棘白菌素耐药所必需的。虽然细胞壁重塑已在葡聚糖或甘露聚糖合成突变体中得到描述，但在几丁质合成突变体中尚未报道。在这里，我们描述了致病性酵母光滑念珠菌的几丁质合成突变体Δchs3A 和 Δchs3B 中的一种新的细胞壁重塑和回收途径。电子显微镜分析显示，Δchs3A 细胞中的甘露糖蛋白层变厚，Δchs3B 细胞中的几丁质-葡聚糖层变厚，这表明了甘露聚糖合酶和几丁质-葡聚糖合酶分别补偿Δchs3A 和 Δchs3B 细胞的假说。编码α-1,6-甘露糖基转移酶的双突变体 CHS3A 和 MNN10 表现出协同应激敏化，而Δchs3B 菌株对棘白菌素表现出超敏性。因此，这些发现支持了上述重塑假说。此外，与Δchs3A 细胞不同，Δchs3B 细胞对钙调神经磷酸酶抑制剂 FK506 和 Tor1p 激酶抑制剂雷帕霉素表现出超敏性，表明Δchs3B 菌株使用钙调神经磷酸酶途径和 Tor1p 激酶进行细胞壁重塑。
