Subunits of the vacuolar H+-ATPase complex, Vma4 and Vma10, are essential for virulence and represent potential drug targets in Candida albicans

Se Woong Kim; Young Kwang Park; Yoo Jin Joo; Yu Jin Chun; Ju Yeon Hwang; Je Hyun Baek; Joon Kim

doi:10.1016/j.funbio.2019.06.002

Subunits of the vacuolar H+-ATPase complex, Vma4 and Vma10, are essential for virulence and represent potential drug targets in Candida albicans

Se Woong Kim, Young Kwang Park, Yoo Jin Joo, Yu Jin Chun, Ju Yeon Hwang, Je Hyun Baek, Joon Kim

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Hyphal morphogenesis of Candida albicans is important for its pathogenesis. Here, we showed that the filamentous growth of C. albicans requires vacuolar H⁺-ATPase function. Results showed that levels of Vma4 and Vma10 increased in cells undergoing hyphal growth compared to those undergoing yeast growth. Deleting VMA4 or VMA10 abolished vacuolar functions and hyphal morphogenesis. These deletion mutants were also characterized as avirulent in a mouse model of systemic infection. Furthermore, VMA4 and VMA10 deletion strains showed hypersensitivity to fluconazole, terbinafine, and amphotericin B. Based on these findings, Vma4 and Vma10 are not only involved in vacuole biogenesis and hyphal formation, but also are good targets for antifungal drug development in C. albicans.

Original language	English
Pages (from-to)	709-722
Number of pages	14
Journal	Fungal Biology
Volume	123
Issue number	10
DOIs	https://doi.org/10.1016/j.funbio.2019.06.002
Publication status	Published - 2019 Oct

Keywords

C. albicans
Candida drug
Morphogenesis
Pathogenesis
V-ATPase

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.funbio.2019.06.002

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title = "Subunits of the vacuolar H+-ATPase complex, Vma4 and Vma10, are essential for virulence and represent potential drug targets in Candida albicans",

abstract = "Hyphal morphogenesis of Candida albicans is important for its pathogenesis. Here, we showed that the filamentous growth of C. albicans requires vacuolar H+-ATPase function. Results showed that levels of Vma4 and Vma10 increased in cells undergoing hyphal growth compared to those undergoing yeast growth. Deleting VMA4 or VMA10 abolished vacuolar functions and hyphal morphogenesis. These deletion mutants were also characterized as avirulent in a mouse model of systemic infection. Furthermore, VMA4 and VMA10 deletion strains showed hypersensitivity to fluconazole, terbinafine, and amphotericin B. Based on these findings, Vma4 and Vma10 are not only involved in vacuole biogenesis and hyphal formation, but also are good targets for antifungal drug development in C. albicans.",

keywords = "C. albicans, Candida drug, Morphogenesis, Pathogenesis, V-ATPase",

author = "Kim, {Se Woong} and Park, {Young Kwang} and Joo, {Yoo Jin} and Chun, {Yu Jin} and Hwang, {Ju Yeon} and Baek, {Je Hyun} and Joon Kim",

note = "Funding Information: This work was supported by a 2017 NRF2017-R1E1A1A01074101 Grant from the Ministry of Science and Technology, Korea. Consulting service from the MCRB (Seoul, Korea) was kindly appreciated. Funding Information: This work was supported by a 2017 NRF2017- R1E1A1A01074101 Grant from the Ministry of Science and Technology, Korea . Consulting service from the MCRB (Seoul, Korea) was kindly appreciated. Publisher Copyright: {\textcopyright} 2019 British Mycological Society",

year = "2019",

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doi = "10.1016/j.funbio.2019.06.002",

language = "English",

volume = "123",

pages = "709--722",

journal = "Fungal Biology",

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AU - Kim, Se Woong

AU - Park, Young Kwang

AU - Joo, Yoo Jin

AU - Chun, Yu Jin

AU - Hwang, Ju Yeon

AU - Baek, Je Hyun

AU - Kim, Joon

N1 - Funding Information: This work was supported by a 2017 NRF2017-R1E1A1A01074101 Grant from the Ministry of Science and Technology, Korea. Consulting service from the MCRB (Seoul, Korea) was kindly appreciated. Funding Information: This work was supported by a 2017 NRF2017- R1E1A1A01074101 Grant from the Ministry of Science and Technology, Korea . Consulting service from the MCRB (Seoul, Korea) was kindly appreciated. Publisher Copyright: © 2019 British Mycological Society

PY - 2019/10

Y1 - 2019/10

N2 - Hyphal morphogenesis of Candida albicans is important for its pathogenesis. Here, we showed that the filamentous growth of C. albicans requires vacuolar H+-ATPase function. Results showed that levels of Vma4 and Vma10 increased in cells undergoing hyphal growth compared to those undergoing yeast growth. Deleting VMA4 or VMA10 abolished vacuolar functions and hyphal morphogenesis. These deletion mutants were also characterized as avirulent in a mouse model of systemic infection. Furthermore, VMA4 and VMA10 deletion strains showed hypersensitivity to fluconazole, terbinafine, and amphotericin B. Based on these findings, Vma4 and Vma10 are not only involved in vacuole biogenesis and hyphal formation, but also are good targets for antifungal drug development in C. albicans.

AB - Hyphal morphogenesis of Candida albicans is important for its pathogenesis. Here, we showed that the filamentous growth of C. albicans requires vacuolar H+-ATPase function. Results showed that levels of Vma4 and Vma10 increased in cells undergoing hyphal growth compared to those undergoing yeast growth. Deleting VMA4 or VMA10 abolished vacuolar functions and hyphal morphogenesis. These deletion mutants were also characterized as avirulent in a mouse model of systemic infection. Furthermore, VMA4 and VMA10 deletion strains showed hypersensitivity to fluconazole, terbinafine, and amphotericin B. Based on these findings, Vma4 and Vma10 are not only involved in vacuole biogenesis and hyphal formation, but also are good targets for antifungal drug development in C. albicans.

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Subunits of the vacuolar H+-ATPase complex, Vma4 and Vma10, are essential for virulence and represent potential drug targets in Candida albicans

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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