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Novel and potent antimicrobial effects of caspofungin on drug-resistant Candida and bacteria

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Title: Novel and potent antimicrobial effects of caspofungin on drug-resistant Candida and bacteria
Authors: Sumiyoshi, Makoto / Miyazaki, Taiga / Makau, Juliann Nzembi / Mizuta, Satoshi / Tanaka, Yoshimasa / Ishikawa, Takeshi / Makimura, Koichi / Hirayama, Tatsuro / Takazono, Takahiro / Saijo, Tomomi / Yamaguchi, Hiroyuki / Shimamura, Shintaro / Yamamoto, Kazuko / Imamura, Yoshifumi / Sakamoto, Noriho / Obase, Yasushi / Izumikawa, Koichi / Yanagihara, Katsunori / Kohno, Shigeru / Mukae, Hiroshi
Issue Date: 20-Oct-2020
Publisher: Springer Nature
Citation: Scientific Reports, 10(1), art.no.17745; 2020
Abstract: chinocandins, including caspofungin, micafungin, and anidulafungin, are first-line antifungal agents for the treatment of invasive candidiasis. They exhibit fungicidal activity by inhibiting the synthesis of β-1,3-d-glucan, an essential component of the fungal cell wall. However, they are active only against proliferating fungal cells and unable to completely eradicate fungal cells even after a 24 h drug exposure in standard time-kill assays. Surprisingly, we found that caspofungin, when dissolved in low ionic solutions, had rapid and potent antimicrobial activities against multidrug-resistant (MDR) Candida and bacteria cells even in non-growth conditions. This effect was not observed in 0.9% NaCl or other ion-containing solutions and was not exerted by other echinocandins. Furthermore, caspofungin dissolved in low ionic solutions drastically reduced mature biofilm cells of MDR Candida auris in only 5 min, as well as Candida-bacterial polymicrobial biofilms in a catheter-lock therapy model. Caspofungin displayed ion concentration-dependent conformational changes and intracellular accumulation with increased reactive oxygen species production, indicating a novel mechanism of action in low ionic conditions. Importantly, caspofungin dissolved in 5% glucose water did not exhibit increased toxicity to human cells. This study facilitates the development of new therapeutic strategies in the management of catheter-related biofilm infections.
URI: http://hdl.handle.net/10069/40377
DOI: 10.1038/s41598-020-74749-8
Rights: © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/40377

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