Proton pump inhibitors act synergistically with fluconazole against resistant Candida albicans.

Abstract:

:The incidence of resistant Candida isolates, especially Candida albicans, has increased continuously. To overcome the resistance, research on antifungal agent sensitizers has attracted considerable attention. Omeprazole and lansoprazole were found to inhibit the growth of sensitive C. albicans and hyphae formation in a high dose, respectively. This study aimed to determine the interactions of common clinically proton pump inhibitors (PPIs) and fluconazole both in vitro and in vivo and to further explore the possible mechanisms. In vitro, the tested PPIs all acted synergistically with fluconazole against both resistant C. albicans planktonic cells and biofilms preformed for ≤12 h with the minimum inhibitory concentration of fluconazole decreased from >512 μg/mL to 1-4 μg/mL. In vivo, PPIs plus fluconazole prolonged the survival rate of infected Galleria mellonella larvae by two-fold compared with that for the fluconazole monotherapy group and significantly reduced the tissue damage of infected larvae. Mechanism studies showed that PPIs significantly suppressed efflux pump activity, which is the common resistance mechanism of C. albicans, and significantly inhibited the virulence factors: phospholipase activity and morphology switching. These findings will provide new insights into antifungal agent discovery and potential approaches for the treatment of candidiasis caused by resistant C. albicans.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Lu M,Yan H,Yu C,Yuan L,Sun S

doi

10.1038/s41598-019-57174-4

subject

Has Abstract

pub_date

2020-01-16 00:00:00

pages

498

issue

1

issn

2045-2322

pii

10.1038/s41598-019-57174-4

journal_volume

10

pub_type

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