Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT In the pathogenic yeast Candida albicans, the DNA damage response contributes to pathogenicity by regulating cell morphology transitions and maintaining survival in response to DNA damage induced by reactive oxygen species (ROS) in host cells. However, the function of nucleotide excision re...

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Autores principales:	Jia Feng, Shuangyan Yao, Yansong Dong, Jing Hu, Malcolm Whiteway, Jinrong Feng
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans Rad23 Rad4 nucleotide excision repair virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0ade4561dbef466899551e04b5a3ae9e
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spelling	oai:doaj.org-article:0ade4561dbef466899551e04b5a3ae9e2021-11-15T15:27:53ZNucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mSphere.00062-202379-5042https://doaj.org/article/0ade4561dbef466899551e04b5a3ae9e2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00062-20https://doaj.org/toc/2379-5042ABSTRACT In the pathogenic yeast Candida albicans, the DNA damage response contributes to pathogenicity by regulating cell morphology transitions and maintaining survival in response to DNA damage induced by reactive oxygen species (ROS) in host cells. However, the function of nucleotide excision repair (NER) in C. albicans has not been extensively investigated. To better understand the DNA damage response and its role in virulence, we studied the function of the Rad23 nucleotide excision repair protein in detail. The RAD23 deletion strain and overexpression strain both exhibit UV sensitivity, confirming the critical role of RAD23 in the nucleotide excision repair pathway. Genetic interaction assays revealed that the role of RAD23 in the UV response relies on RAD4 but is independent of RAD53, MMS22, and RAD18. RAD4 and RAD23 have similar roles in regulating cell morphogenesis and biofilm formation; however, only RAD23, but not RAD4, plays a negative role in virulence regulation in a mouse model. We found that the RAD23 deletion strain showed decreased survival in a Candida-macrophage interaction assay. Transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) data further revealed that RAD23, but not RAD4, regulates the transcription of a virulence factor, SUN41, suggesting a unique role of RAD23 in virulence regulation. Taking these observations together, our work reveals that the RAD23-related nucleotide excision pathway plays a critical role in the UV response but may not play a direct role in virulence. The virulence-related role of RAD23 may rely on the regulation of several virulence factors, which may give us further understanding about the linkage between DNA damage repair and virulence regulation in C. albicans. IMPORTANCE Candida albicans remains a significant threat to the lives of immunocompromised people. An understanding of the virulence and infection ability of C. albicans cells in the mammalian host may help with clinical treatment and drug discovery. The DNA damage response pathway is closely related to morphology regulation and virulence, as well as the ability to survive in host cells. In this study, we checked the role of the nucleotide excision repair (NER) pathway, the key repair system that functions to remove a large variety of DNA lesions such as those caused by UV light, but whose function has not been well studied in C. albicans. We found that Rad23, but not Rad4, plays a role in virulence that appears independent of the function of the NER pathway. Our research revealed that the NER pathway represented by Rad4/Rad23 may not play a direct role in virulence but that Rad23 may play a unique role in regulating the transcription of virulence genes that may contribute to the virulence of C. albicans.Jia FengShuangyan YaoYansong DongJing HuMalcolm WhitewayJinrong FengAmerican Society for MicrobiologyarticleCandida albicansRad23Rad4nucleotide excision repairvirulenceMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Rad23 Rad4 nucleotide excision repair virulence Microbiology QR1-502
spellingShingle	Candida albicans Rad23 Rad4 nucleotide excision repair virulence Microbiology QR1-502 Jia Feng Shuangyan Yao Yansong Dong Jing Hu Malcolm Whiteway Jinrong Feng Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>
description	ABSTRACT In the pathogenic yeast Candida albicans, the DNA damage response contributes to pathogenicity by regulating cell morphology transitions and maintaining survival in response to DNA damage induced by reactive oxygen species (ROS) in host cells. However, the function of nucleotide excision repair (NER) in C. albicans has not been extensively investigated. To better understand the DNA damage response and its role in virulence, we studied the function of the Rad23 nucleotide excision repair protein in detail. The RAD23 deletion strain and overexpression strain both exhibit UV sensitivity, confirming the critical role of RAD23 in the nucleotide excision repair pathway. Genetic interaction assays revealed that the role of RAD23 in the UV response relies on RAD4 but is independent of RAD53, MMS22, and RAD18. RAD4 and RAD23 have similar roles in regulating cell morphogenesis and biofilm formation; however, only RAD23, but not RAD4, plays a negative role in virulence regulation in a mouse model. We found that the RAD23 deletion strain showed decreased survival in a Candida-macrophage interaction assay. Transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) data further revealed that RAD23, but not RAD4, regulates the transcription of a virulence factor, SUN41, suggesting a unique role of RAD23 in virulence regulation. Taking these observations together, our work reveals that the RAD23-related nucleotide excision pathway plays a critical role in the UV response but may not play a direct role in virulence. The virulence-related role of RAD23 may rely on the regulation of several virulence factors, which may give us further understanding about the linkage between DNA damage repair and virulence regulation in C. albicans. IMPORTANCE Candida albicans remains a significant threat to the lives of immunocompromised people. An understanding of the virulence and infection ability of C. albicans cells in the mammalian host may help with clinical treatment and drug discovery. The DNA damage response pathway is closely related to morphology regulation and virulence, as well as the ability to survive in host cells. In this study, we checked the role of the nucleotide excision repair (NER) pathway, the key repair system that functions to remove a large variety of DNA lesions such as those caused by UV light, but whose function has not been well studied in C. albicans. We found that Rad23, but not Rad4, plays a role in virulence that appears independent of the function of the NER pathway. Our research revealed that the NER pathway represented by Rad4/Rad23 may not play a direct role in virulence but that Rad23 may play a unique role in regulating the transcription of virulence genes that may contribute to the virulence of C. albicans.
format	article
author	Jia Feng Shuangyan Yao Yansong Dong Jing Hu Malcolm Whiteway Jinrong Feng
author_facet	Jia Feng Shuangyan Yao Yansong Dong Jing Hu Malcolm Whiteway Jinrong Feng
author_sort	Jia Feng
title	Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>
title_short	Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>
title_full	Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr	Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed	Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>
title_sort	nucleotide excision repair protein rad23 regulates cell virulence independent of rad4 in <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/0ade4561dbef466899551e04b5a3ae9e
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Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in <named-content content-type="genus-species">Candida albicans</named-content>

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