Unique roles of aminophospholipid translocase Drs2p in governing efflux pump activity, ergosterol level, virulence traits, and host–pathogen interaction in Candida albicans
Infections caused by Candida albicans are rising due to increment in drug resistance and a limited arsenal of conventional antifungal drugs. Thus, elucidating the novel antifungal targets still represent an alternative that could overcome the problem of multidrug resistance (MDR). In this study, we...
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Published in | International microbiology Vol. 25; no. 4; pp. 769 - 779 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.11.2022
Spanish Society for Microbiology |
Subjects | |
Online Access | Get full text |
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Summary: | Infections caused by
Candida albicans
are rising due to increment in drug resistance and a limited arsenal of conventional antifungal drugs. Thus, elucidating the novel antifungal targets still represent an alternative that could overcome the problem of multidrug resistance (MDR). In this study, we have uncovered the distinctive effect of aminophospholipid translocase (Drs2p) deletion on major MDR mechanisms of
C. albicans
. We determined that efflux activity was diminished in
Δdrs2
mutant as revealed by extracellular rhodamine 6G (R6G) efflux and flow cytometry. Moreover, we further unveiled that
Δdrs2
mutant displayed decreased ergosterol content and increased membrane fluidity. Furthermore, Drs2p deletion affects the virulence attributes and led to inhibited hyphal growth and reduced biofilm formation. Additionally, THP-1 cell lines’ mediated host–pathogen interaction studies revealed that
Δdrs2
mutant displayed enhanced phagocytosis and altered cytokine production leading to increased IL-6 and decreased IL-10 production. Taken together, the present study demonstrates the relevance of Drs2p in
C. albicans
and consequently disrupting pathways known for mediating drug resistance and immune recognition. Comprehensive studies are further required to authenticate Drs2p as a novel antifungal drug target. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1618-1905 1139-6709 1618-1905 |
DOI: | 10.1007/s10123-022-00262-9 |