In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species

Ten <i>Candida</i> species strains were isolated from the first known fatal case of rhinofacial and rhino–orbital–cerebral candidiasis. Among them, five strains of <i>Candida parapsilosis</i> complex were isolated during the early stage of hospitalization, while five strains...

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Main Authors: Yuchen Wang, Xi Guo, Xinran Zhang, Ping Chen, Wenhui Wang, Shan Hu, Teng Ma, Xingchen Zhou, Dongming Li, Ying Yang
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/9/8/815
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author Yuchen Wang
Xi Guo
Xinran Zhang
Ping Chen
Wenhui Wang
Shan Hu
Teng Ma
Xingchen Zhou
Dongming Li
Ying Yang
author_facet Yuchen Wang
Xi Guo
Xinran Zhang
Ping Chen
Wenhui Wang
Shan Hu
Teng Ma
Xingchen Zhou
Dongming Li
Ying Yang
author_sort Yuchen Wang
collection DOAJ
description Ten <i>Candida</i> species strains were isolated from the first known fatal case of rhinofacial and rhino–orbital–cerebral candidiasis. Among them, five strains of <i>Candida parapsilosis</i> complex were isolated during the early stage of hospitalization, while five strains of <i>Candida tropicalis</i> were isolated in the later stages of the disease. Using whole-genome sequencing, we distinguished the five strains of <i>C</i>. <i>parapsilosis</i> complex as four <i>Candida metapsilosis</i> strains and one <i>Candida parapsilosis</i> strain. Antifungal susceptibility testing showed that the five strains of <i>C. parapsilosis</i> complex were susceptible to all antifungal drugs, while five <i>C. tropicalis</i> strains had high minimum inhibitory concentrations to azoles, whereas antifungal-drug resistance gene analysis revealed the causes of azole resistance in such strains. For the first time, we analyzed the microevolutionary characteristics of pathogenic fungi in human hosts and inferred the infection time and parallel evolution of <i>C. tropicalis</i> strains. Molecular clock analysis revealed that azole-resistant <i>C. tropicalis</i> infection occurred during the first round of therapy, followed by divergence via parallel evolution in vivo. The presence/absence variations indicated a potential decrease in the virulence of genomes in strains isolated following antifungal drug treatment, despite the absence of observed clinical improvement in the conditions of the patient. These results suggest that genomic analysis could serve as an auxiliary tool in guiding clinical diagnosis and treatment.
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spelling doaj.art-c96776ba60d14bd9ad0da718d3eb19602023-11-19T01:47:25ZengMDPI AGJournal of Fungi2309-608X2023-08-019881510.3390/jof9080815In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida SpeciesYuchen Wang0Xi Guo1Xinran Zhang2Ping Chen3Wenhui Wang4Shan Hu5Teng Ma6Xingchen Zhou7Dongming Li8Ying Yang9Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, ChinaTEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjing 300457, ChinaBioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, ChinaDivision of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing 100191, ChinaDivision of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing 100191, ChinaBioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, ChinaBioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, ChinaBioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, ChinaDivision of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing 100191, ChinaBioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, ChinaTen <i>Candida</i> species strains were isolated from the first known fatal case of rhinofacial and rhino–orbital–cerebral candidiasis. Among them, five strains of <i>Candida parapsilosis</i> complex were isolated during the early stage of hospitalization, while five strains of <i>Candida tropicalis</i> were isolated in the later stages of the disease. Using whole-genome sequencing, we distinguished the five strains of <i>C</i>. <i>parapsilosis</i> complex as four <i>Candida metapsilosis</i> strains and one <i>Candida parapsilosis</i> strain. Antifungal susceptibility testing showed that the five strains of <i>C. parapsilosis</i> complex were susceptible to all antifungal drugs, while five <i>C. tropicalis</i> strains had high minimum inhibitory concentrations to azoles, whereas antifungal-drug resistance gene analysis revealed the causes of azole resistance in such strains. For the first time, we analyzed the microevolutionary characteristics of pathogenic fungi in human hosts and inferred the infection time and parallel evolution of <i>C. tropicalis</i> strains. Molecular clock analysis revealed that azole-resistant <i>C. tropicalis</i> infection occurred during the first round of therapy, followed by divergence via parallel evolution in vivo. The presence/absence variations indicated a potential decrease in the virulence of genomes in strains isolated following antifungal drug treatment, despite the absence of observed clinical improvement in the conditions of the patient. These results suggest that genomic analysis could serve as an auxiliary tool in guiding clinical diagnosis and treatment.https://www.mdpi.com/2309-608X/9/8/815fungimicroevolutiongeneticscandidiasisrhinofacial and rhino–orbital–cerebral mycosis
spellingShingle Yuchen Wang
Xi Guo
Xinran Zhang
Ping Chen
Wenhui Wang
Shan Hu
Teng Ma
Xingchen Zhou
Dongming Li
Ying Yang
In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species
Journal of Fungi
fungi
microevolution
genetics
candidiasis
rhinofacial and rhino–orbital–cerebral mycosis
title In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species
title_full In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species
title_fullStr In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species
title_full_unstemmed In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species
title_short In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species
title_sort in vivo microevolutionary analysis of a fatal case of rhinofacial and disseminated mycosis due to azole drug resistant candida species
topic fungi
microevolution
genetics
candidiasis
rhinofacial and rhino–orbital–cerebral mycosis
url https://www.mdpi.com/2309-608X/9/8/815
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