First two fungemia cases caused by Candida haemulonii var. vulnera in China with emerged antifungal resistance

Xin-Fei Chen; Xin Hou; Han Zhang; Xin-Miao Jia; Li-Ping Ning; Wei Cao; Xin Fan; Jing-Jing Huang; Wen-Hang Yang; Ge Zhang; Jing-Jia Zhang; Wei Kang; Meng Xiao; Ying-Chun Xu

doi:10.3389/fmicb.2022.1036351

First two fungemia cases caused by Candida haemulonii var. vulnera in China with emerged antifungal resistance

Front Microbiol. 2022 Nov 10:13:1036351. doi: 10.3389/fmicb.2022.1036351. eCollection 2022.

Authors

Xin-Fei Chen^{1

2

3}, Xin Hou⁴, Han Zhang^{1

3}, Xin-Miao Jia^{3

5}, Li-Ping Ning⁶, Wei Cao⁷, Xin Fan⁸, Jing-Jing Huang^{1

2

3}, Wen-Hang Yang^{1

3}, Ge Zhang^{1

3}, Jing-Jia Zhang^{1

3}, Wei Kang^{1

3}, Meng Xiao^{1

3}, Ying-Chun Xu^{1

3}

Affiliations

¹ Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China.
⁴ Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China.
⁵ Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁶ Department of Laboratory Medicine, No.908 Hospital of Joint Logistics Support Force, Nanchang, Jiangxi, China.
⁷ Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hubei, China.
⁸ Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Abstract

Candida haemulonii var. vulnera is a rare variant of C. haemulonii, which has been previously reported to cause human infections. Owing to the close kinship between C. haemulonii sensu stricto and C. haemulonii var. vulnera, accurate identification of C. haemulonii var. vulnera relied on DNA sequencing assay targeting, for example, rDNA internal transcribed spacer (ITS) region. In this work, two strains of C. haemulonii var. vulnera were collected from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET). The identification capacity of three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 YST ID biochemical methods were evaluated against ITS sequencing. In addition, antifungal susceptibility testing was performed using Sensititre YeastOne. Moreover, we comprehensively screened drug-resistant related genes by whole-genome sequencing. The two strains were not correctly identified to species variant level using MALDI-TOF MS and YST ID cards. Both strains were resistant to amphotericin B (minimum inhibitory concentration [MIC] > 2 μg/ml). Moreover, strain F4564 and F4584 exhibited high MIC to fluconazole (>256 μg/ml) and 5-flucytosine (>64 μg/ml), respectively, which were supposed to result from key amino acid substitutions Y132F and G307A in Erg11p and V58fs and G60K substitutions in Fur1p. The rare species C. haemulonii var. vulnera has emerged in China, and such drug-resistant fungal species that can cause invasive diseases require further close attention.

Keywords: Candida haemulonii var. vulnera; ERG11; FUR1; antifungal susceptibility; drug resistant mechanisms; whole-genome sequence.

Grants and funding

This study was supported by the National Key Research and Development Program of China (2022YFC2300017), National Natural Science Foundation of China (82002178), National High Level Hospital Clinical Research Funding (2022-PUMCH-B-074), Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program (Grant No. 20191080604), Beijing Key Clinical Specialty for Laboratory Medicine-Excellent Project (No. ZK201000), and CAMS Innovation Fund for Medical Sciences (2021-I2M-1-038 and 2021-I2M-1-044).