Contribution of the Slt2-regulated transcription factors to echinocandin tolerance in Candida glabrata.
Contribution of the Slt2-regulated transcription factors to echinocandin tolerance in Candida glabrata.
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Slt2 调节的转录因子对光滑念珠菌棘白菌素耐受性的贡献。
DOI：
10.1111/1567-1364.12204
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发表时间：
2014
影响因子：
3.2
通讯作者：
Kohno S.
中科院分区：
文献类型：
--
作者：
Nagayoshi Y;Miyazaki T;Minematsu A;Yamauchi S;Takazono T;Nakamura S;Imamura Y;Izumikawa K;Kakeya H;Yanagihara K;Kohno S.
棘白菌素类抗真菌药物，包括米卡芬净，被认为是治疗光滑念珠菌感染的一线药物。然而，最近的流行病学调查显示，越来越多的C。显示棘白菌素亲和性降低的光滑分离物。Slt 2丝裂原活化蛋白激酶途径对于真菌细胞壁完整性的维持是重要的。Rlm 1和Swi 4-Swi 6细胞周期盒结合因子（SBF）是Slt 2下游的转录因子。虽然Slt 2和Rlm 1在响应细胞壁应激（如米卡芬净暴露）中起重要作用，但对SBF inC知之甚少。光滑的在这里，我们生成了C。光滑的菌株缺乏或过表达SWI 4和SWI 6，并评估其对米卡芬净的敏感性。米卡芬净耐受性在️ swi 4菌株中显着降低，而在过表达SWI 4的菌株中增加。另一方面，SWI 6的缺失轻微损害米卡芬净耐受性，但SWI 6的过表达没有影响。这些结果表明，虽然Swi 4和Swi 6形成蛋白复合物，但Swi 4比Swi 6更主要地参与米卡芬净耐受性。光滑的此外，RLM 1的过表达诱导了野生型背景下米卡芬净耐受性的增加，但在Escheroswi 4和Escheroswi 6菌株中没有，这表明Rlm 1和SBF在米卡芬净暴露的反应中相互依赖地起作用。
Echinocandin-class antifungals, including micafungin, are considered as the first-line treatment forCandida glabratainfections. However, recent epidemiological surveys have revealed an increasing number ofC. glabrataisolates exhibiting decreased echinocandin susceptibilities. The Slt2 mitogen-activated protein kinase pathway is important for maintenance of cell wall integrity in fungi. Rlm1 and Swi4–Swi6 cell cycle box binding factor (SBF) are transcription factors downstream of Slt2. While Slt2 and Rlm1 play important roles in response to cell wall stresses, such as micafungin exposure, little is known about SBF inC. glabrata. Here, we generatedC. glabratastrains lacking or overexpressingSWI4andSWI6and evaluated their susceptibilities to micafungin. Micafungin tolerance considerably decreased in the ∆swi4strain, whereas it increased in the strains overexpressingSWI4. On the other hand, deletion ofSWI6slightly impaired micafungin tolerance, but overexpression ofSWI6had no effect. These results suggest that, although Swi4 and Swi6 form a protein complex, Swi4 is involved in micafungin tolerance more predominantly than Swi6 inC. glabrata. Furthermore, the overexpression ofRLM1induced increased micafungin tolerance in the wild-type background but not in the ∆swi4and ∆swi6strains, suggesting that Rlm1 and SBF function interdependently in response to micafungin exposure.
影响因子：
11.8
作者：
Alexander, Barbara D.;Johnson, Melissa D.;Pfaller, Michael A.
通讯作者：
Pfaller, Michael A.
机会性酵母病原体光滑念珠菌中的高效同源和非法重组。
影响因子：
3.3
作者：
B. Cormack;S. Falkow;S. Falkow
通讯作者：
S. Falkow
影响因子：
3.2
作者：
Miyazaki, Taiga;Izumikawa, Koichi;Kohno, Shigeru
通讯作者：
Kohno, Shigeru