Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans

Jie Gong; Xin-Fei Chen; Xin Fan; Juan Xu; Han Zhang; Ruo-Yu Li; Sharon C-A Chen; Fanrong Kong; Shu Zhang; Zi-Yong Sun; Mei Kang; Kang Liao; Da-Wen Guo; Zhe Wan; Zhi-Dong Hu; Yun-Zhuo Chu; Hong-Mei Zhao; Gui-Ling Zou; Chong Shen; Yuan-Yuan Geng; Wei-Wei Wu; He Wang; Fei Zhao; Xin Lu; Li-Hua He; Gui-Ming Liu; Ying-Chun Xu; Jian-Zhong Zhang; Meng Xiao

doi:10.1128/spectrum.03807-22

Microbiology Spectrum (Feb 2023)

Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans

Jie Gong,
Xin-Fei Chen,
Xin Fan,
Juan Xu,
Han Zhang,
Ruo-Yu Li,
Sharon C-A Chen,
Fanrong Kong,
Shu Zhang,
Zi-Yong Sun,
Mei Kang,
Kang Liao,
Da-Wen Guo,
Zhe Wan,
Zhi-Dong Hu,
Yun-Zhuo Chu,
Hong-Mei Zhao,
Gui-Ling Zou,
Chong Shen,
Yuan-Yuan Geng,
Wei-Wei Wu,
He Wang,
Fei Zhao,
Xin Lu,
Li-Hua He,
Gui-Ming Liu,
Ying-Chun Xu,
Jian-Zhong Zhang,
Meng Xiao

Affiliations

Jie Gong: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Xin-Fei Chen: Department of Laboratory Medicine, Sate Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
Xin Fan: Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Juan Xu: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Han Zhang: Department of Laboratory Medicine, Sate Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
Ruo-Yu Li: Department of Dermatology, Beijing University First Hospital, Beijing, China
Sharon C-A Chen: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
Fanrong Kong: Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
Shu Zhang: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Zi-Yong Sun: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Mei Kang: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
Kang Liao: Department of Clinical Laboratory, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Da-Wen Guo: Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
Zhe Wan: Department of Dermatology, Beijing University First Hospital, Beijing, China
Zhi-Dong Hu: Department of Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin, China
Yun-Zhuo Chu: Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
Hong-Mei Zhao: Department of Clinical Laboratory, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China
Gui-Ling Zou: Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
Chong Shen: Center for Statistical Science, and Department of Industrial Engineering, Tsinghua University, Beijing, China
Yuan-Yuan Geng: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Wei-Wei Wu: Department of Dermatology, the Fifth People's Hospital of Hainan Province, Haikou, Hainan, China
He Wang: Dynamiker Sub-center of Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Disease, Tianjin, China
Fei Zhao: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Xin Lu: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Li-Hua He: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Gui-Ming Liu: Beijing Agro-Biotechnology Research Center, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China
Ying-Chun Xu: Department of Laboratory Medicine, Sate Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
Jian-Zhong Zhang: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Meng Xiao: Department of Laboratory Medicine, Sate Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

DOI: https://doi.org/10.1128/spectrum.03807-22
Journal volume & issue: Vol. 11, no. 1

Abstract

Read online

ABSTRACT Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

About the journal

Abstract

Keywords