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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2023-08-01
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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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