Antifungal Susceptibility Profiles and Resistance Mechanisms of Clinical Diutina catenulata Isolates With High MIC Values

Frontiers in Cellular and Infection Microbiology

Bin Li¹  Yu-Hong Pan¹  Hong He²  Xin Fan³  Ying-Xing Li⁴  Jin-Wen Wang⁵  Xin Hou⁶  Han Zhang⁶  Ge Zhang⁶  Xiao-Yu Liu⁶  Wei Kang⁶  Ying-Chun Xu⁶  Jing-Jing Huang⁷  Xin-Fei Chen⁷  Wen-Hang Yang⁷  Wei Zhang⁸  Da-Wen Guo⁹  Xue-Fei Du^1,10  Ling-Gui Zou^1,10  Zi-Yong Sun^1,11  Zhong-Ju Chen^1,11 

[1] Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China;Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China;Department of Laboratory Medicine, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China;Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Beijing, China;Department of Laboratory Medicine, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China;Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China;Department of Laboratory Medicine, Daqing Oilfield General Hospital, Daqing, China;Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China;Department of Laboratory Medicine, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China;Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China;Graduate School, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China;Department of Laboratory Medicine, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China;Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China;Graduate School, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China;Department of Laboratory Medicine, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China;Clinical Microbiology Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China;Department of Laboratory Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, China;Department of Laboratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China;Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;

关键词: Diutina catenulata;    antifungal susceptibility;    ERG11;    FKS1;    gene mutation;    drug resistance mechanisms;   

DOI  :  10.3389/fcimb.2021.739496

来源: Frontiers

【 摘 要 】

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06–0.12 μg/ml), posaconazole (0.06–0.12 μg/ml), amphotericin B (0.25–1 μg/ml), and 5-flucytosine (range, <0.06–0.12 μg/ml), whereas four isolates showed high MICs (≥4 μg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.

【 授权许可】

CC BY