Candida albicans Multilocus Sequence Typing Clade I Contributes to the Clinical Phenotype of Vulvovaginal Candidiasis Patients

Yuxia Zhu; Chao Fang; Yu Shi; Yingying Shan; Xiaoping Liu; Yiheng Liang; Liting Huang; Xinyang Liu; Chunfeng Liu; Yin Zhao; Shangrong Fan; Xiaowei Zhang

doi:10.3389/fmed.2022.837536

Candida albicans Multilocus Sequence Typing Clade I Contributes to the Clinical Phenotype of Vulvovaginal Candidiasis Patients

Front Med (Lausanne). 2022 Apr 1:9:837536. doi: 10.3389/fmed.2022.837536. eCollection 2022.

Authors

Yuxia Zhu^{1

2

3}, Chao Fang⁴, Yu Shi⁵, Yingying Shan^{1

2

3}, Xiaoping Liu⁶, Yiheng Liang^{1

2

3}, Liting Huang^{1

2

3}, Xinyang Liu^{1

2

3}, Chunfeng Liu^{1

2

3}, Yin Zhao⁷, Shangrong Fan^{1

2

3}, Xiaowei Zhang^{1

2

3}

Affiliations

¹ Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China.
² Shenzhen PKU-HKUST Medical Center, Institute of Obstetrics and Gynecology, Shenzhen, China.
³ Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Disease, Shenzhen, China.
⁴ BGI-Shenzhen, Shenzhen, China.
⁵ Clinical College of Peking University Shenzhen Hospital, Anhui Medical University, Hefei, China.
⁶ Department of Laboratory Science, Peking University Shenzhen Hospital, Shenzhen, China.
⁷ Research Institute of Huazhong University of Science and Technology in Shenzhen, Shenzhen, China.

Abstract

Candida albicans is the most frequent fungal species responsible for vulvovaginal candidiasis (VVC), which exhibits distinct genetic diversity that is linked with the clinical phenotype. This study aimed to assess the genotypes and clinical characteristics of different C. albicans isolates from VVC patients. Based on multilocus sequence typing (MLST), clade 1 was identified as the largest C. albicans group, which appeared most frequently in recurrent VVC and treatment failure cases. Further study of antifungal susceptibility demonstrated that MLST clade 1 strains presented significantly higher drug resistance ability than non-clade 1 strains, which result from the overexpression of MDR1. The mRNA and protein expression levels of virulence-related genes were also significantly higher in clade 1 isolates than in non-clade 1 isolates. Proteomic analysis indicated that the protein stabilization pathway was significantly enriched in clade 1 strains and that RPS4 was a central regulator of proteins involved in stress resistance, adherence, and DNA repair, which all contribute to the resistance and virulence of MLST clade 1 strains. This study was the first attempt to compare the correlation mechanisms between C. albicans MLST clade 1 and non-clade 1 strains and the clinical phenotype, which is of great significance for VVC classification and treatment.

Keywords: Candida albicans; antifungal resistance; clinical characterization; multilocus sequence typing; virulence.