Contribution of the Slt2‐regulated transcription factors to echinocandin tolerance in Candida glabrata. Issue 7 (19th September 2014)

• Record Type: Journal Article
• Authors: Nagayoshi, Yohsuke; Miyazaki, Taiga; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Imamura, Yoshifumi; Izumikawa, Koichi; Kakeya, Hiroshi; Yanagihara, Katsunori; Kohno, Shigeru
• Is Part Of: FEMS yeast research. Volume 14:Issue 7(2014)
• Page Start: 1128
• Page End: 1131
• Publication Date: 2014-09-19
• Subjects: Yeast -- Periodicals; Yeasts -- Periodicals; 579.562
• DOI: 10.1111/1567-1364.12204
• Languages: English
• ISSNs: 1567-1356

Abstract

<abstract abstract-type="main" id="fyr12204-abs-0001"> <title>Abstract</title> <p>Echinocandin‐class antifungals, including micafungin, are considered as the first‐line treatment for <italic>Candida glabrata</italic> infections. However, recent epidemiological surveys have revealed an increasing number of <italic>C. glabrata</italic> isolates 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 in <italic>C. glabrata</italic>. Here, we generated <italic>C. glabrata</italic> strains lacking or overexpressing <italic>SWI4</italic> and <italic>SWI6</italic> and evaluated their susceptibilities to micafungin. Micafungin tolerance considerably decreased in the ∆<italic>swi4</italic> strain, whereas it increased in the strains overexpressing <italic>SWI4</italic>. On the other hand, deletion of <italic>SWI6</italic> slightly impaired micafungin tolerance, but overexpression of <italic>SWI6</italic> had no effect. These results suggest that, although Swi4 and Swi6 form a protein complex, Swi4 is involved in micafungin tolerance more predominantly than Swi6 in <italic>C. glabrata</italic>. Furthermore, the overexpression of <italic>RLM1</italic> induced increased micafungin tolerance in the wild‐type background but not in the ∆<italic>swi4</italic> and ∆<italic>swi6</italic> strains, suggesting that Rlm1 and SBF function interdependently in response to micafungin exposure.</p> </abstract>