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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-10-20

AUTHORS

Makoto Sumiyoshi, Taiga Miyazaki, Juliann Nzembi Makau, Satoshi Mizuta, Yoshimasa Tanaka, Takeshi Ishikawa, Koichi Makimura, Tatsuro Hirayama, Takahiro Takazono, Tomomi Saijo, Hiroyuki Yamaguchi, Shintaro Shimamura, Kazuko Yamamoto, Yoshifumi Imamura, Noriho Sakamoto, Yasushi Obase, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae

ABSTRACT

Echinocandins, 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. More... »

PAGES

17745

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-74749-8

DOI

http://dx.doi.org/10.1038/s41598-020-74749-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1131892908

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33082485


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