Gemini quaternary ammonium compound PMT12-BF4 inhibits Candida albicans via regulating iron homeostasis

Li-Hang Hsu , Dobrawa Kwaśniewska , Shih-Cheng Wang , Tang-Long Shen , Daria Wieczorek , Ying-Lien Chen

Abstract

Quaternary ammonium compounds (QACs) are classifed as cationic surfactants, and are known for their biocidal activity. However, their modes of action are thus far not completely understood. In this study, we synthesized a gemini QAC, PMT12-BF4 and found that it exerted unsurpassed broadspectrum antifungal activity against drug susceptible and resistant Candida albicans, and other pathogenic fungi, with a minimal inhibitory concentration (MIC) at 1 or 2μg/mL. These results indicated that PMT12-BF4 used a mode of action distinct from current antifungal drugs. In addition, fungal pathogens treated with PMT12-BF4 were not able to grow on fresh YPD agar plates, indicating that the efect of PMT12-BF4 was fungicidal, and the minimal fungicidal concentration (MFC) against C. albicans isolates was 1 or 2μg/mL. The ability of yeast-to-hyphal transition and bioflm formation of C. albicans was disrupted by PMT12-BF4. To investigate the modes of action of PMT12-BF4 in C. albicans, we used an RNA sequencing approach and screened a C. albicans deletion mutant library to identify potential pathways afected by PMT12-BF4. Combining these two approaches with a spotting assay, we showed that the ability of PMT12-BF4 to inhibit C. albicans is potentially linked to iron ion homeostasis.
Author Li-Hang Hsu
Li-Hang Hsu,,
-
, Dobrawa Kwaśniewska (WT / KTiAI)
Dobrawa Kwaśniewska,,
- Department of Technology and Instrumental Analysis
, Shih-Cheng Wang
Shih-Cheng Wang,,
-
, Tang-Long Shen - National Taiwan University
Tang-Long Shen ,,
-
, Daria Wieczorek (WT / KTiAI)
Daria Wieczorek,,
- Department of Technology and Instrumental Analysis
, Ying-Lien Chen - National Taiwan University
Ying-Lien Chen ,,
-
Journal seriesScientific Reports, ISSN 2045-2322, (N/A 140 pkt)
Issue year2020
No10
Pages1-12
Publication size in sheets0.5
Article number2911
Keywords in Polishgeminalne czwartorzędowe sole amoniowe, Candida albicans
Keywords in Englishgemini quaternary ammonium compound, Candida albicans
ASJC Classification1000 Multidisciplinary
DOIDOI:10.1038/s41598-020-59750-5
URL https://www.nature.com/articles/s41598-020-59750-5
Languageen angielski
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 30-06-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.401; WoS Impact Factor: 2018 = 4.011 (2) - 2018=4.525 (5)
Citation count*1 (2020-09-22)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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