单位：[1]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.[2]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.[3]Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China.[4]Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.北京朝阳医院[5]Department of Dermatology, Beijing University First Hospital, Beijing, China.[6]Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.[7]Research Center for Medical Mycology, Beijing University, Beijing, China.[8]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.[9]Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.检验科华中科技大学同济医学院附属同济医院[10]Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[11]Department of Clinical Laboratory, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.中山大学附属第一医院[12]Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.[13]Department of Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin, China.[14]Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China.[15]Department of Clinical Laboratory, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China.[16]Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.[17]Center for Statistical Science, and Department of Industrial Engineering, Tsinghua University, Beijing, China.[18]Department of Dermatology, the Fifth People's Hospital of Hainan Province, Haikou, Hainan, China.[19]Dynamiker Sub-center of Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Disease, Tianjin, China.[20]Beijing Agro-Biotechnology Research Center, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.
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.
基金：
National Key Research and
Development Program of China (grant no. 2022YFC2303002), the Beijing Nova Program
(Z201100006820127) and the Tsinghua University-Peking Union Medical College Hospital
Initiative Scientific Research Program (20191080604) to M.X., the National Science and
Technology Basic Resource Investigation Special Program of China (2019FY101200) to
Y.C.X., and the National Key R&D Program of China (2018YFC1603800) to J.G.
第一作者单位：[1]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.
共同第一作者：
通讯作者：
通讯机构：[2]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.[3]Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China.
推荐引用方式(GB/T 7714)：
Gong Jie,Chen Xin-Fei,Fan Xin,et al.Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans[J].MICROBIOLOGY SPECTRUM.2023,11(1):doi:10.1128/spectrum.03807-22.
APA：
Gong Jie,Chen Xin-Fei,Fan Xin,Xu Juan,Zhang Han...&Xiao Meng.(2023).Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.MICROBIOLOGY SPECTRUM,11,(1)
MLA：
Gong Jie,et al."Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans".MICROBIOLOGY SPECTRUM 11..1(2023)
生物学