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

Abstract:

:Quaternary ammonium compounds (QACs) are classified 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 broad-spectrum antifungal activity against drug susceptible and resistant Candida albicans, and other pathogenic fungi, with a minimal inhibitory concentration (MIC) at 1 or 2 μg/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 effect of PMT12-BF4 was fungicidal, and the minimal fungicidal concentration (MFC) against C. albicans isolates was 1 or 2 μg/mL. The ability of yeast-to-hyphal transition and biofilm 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 affected 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Hsu LH,Kwaśniewska D,Wang SC,Shen TL,Wieczorek D,Chen YL

doi

10.1038/s41598-020-59750-5

subject

Has Abstract

pub_date

2020-02-19 00:00:00

pages

2911

issue

1

issn

2045-2322

pii

10.1038/s41598-020-59750-5

journal_volume

10

pub_type

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