Vrinda Sharma, Sourav Das, Bram Spruijtenburg, Theun de Groot, Eelco Meijer, Harsimran Kaur, Shivaprakash M Rudramurthy, Anup Ghosh
{"title":"印度北部一家三级医院7年来收集的假丝酵母菌临床分离株氟康唑耐药的基因型多样性和分子基础","authors":"Vrinda Sharma, Sourav Das, Bram Spruijtenburg, Theun de Groot, Eelco Meijer, Harsimran Kaur, Shivaprakash M Rudramurthy, Anup Ghosh","doi":"10.1111/myc.70062","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The recent rise in the global incidence of fluconazole resistance in C. parapsilosis has become a significant public health concern. Epidemiological studies suggest that fluconazole resistance in C. parapsilosis spreads through endemic clones. We, therefore, investigated the molecular epidemiology of fluconazole-resistant C. parapsilosis in our centre.</p><p><strong>Methods: </strong>C. parapsilosis isolates from 2016 through 2022 were investigated for antifungal susceptibility. Fluconazole-resistant isolates were analysed for ERG11 mutation using Sanger sequencing. Gene expression profiles of ERG11, CDR1 and MDR1 were assessed by real-time qPCR. The epidemiological relationship of resistant and susceptible isolates of C. parapsilosis was investigated using short tandem repeat typing. Additionally, biofilm production and cell wall ergosterol contents were also quantified and compared.</p><p><strong>Results: </strong>Among 572 C. parapsilosis isolates, 48 (8.4%) were resistant to fluconazole. Of 28 recoverable resistant isolates, 17.9% (5/28) were wild-type and 82.1% (23/28) harboured the following ERG11 mutations: Y132F (n = 3), K143R (n = 10) and K143R + R398I (10/28). Significant fold-changes were observed in ERG11 (p = 0.037) and MDR1 (p = 0.008) gene expressions in fluconazole resistant compared to susceptible isolates. Contrary to global reports, STR typing suggested a limited clonal transmission of resistant C. parapsilosis with multiple introductions of resistant isolates in our centre. On fluconazole exposure, ergosterol content significantly increased (p < 0.01) in resistant isolates, particularly in isolates harbouring ERG11<sup>K143R + R398I</sup> mutations. In contrast, fluconazole-susceptible isolates formed comparatively higher baseline biofilm (p < 0.05) than resistant isolates with ERG11<sup>K143R</sup> mutation.</p><p><strong>Conclusion: </strong>The current study underscores the need for continuous molecular surveillance and tailored therapeutic options for effective management of fluconazole resistance in C. parapsilosis.</p>","PeriodicalId":18797,"journal":{"name":"Mycoses","volume":"68 5","pages":"e70062"},"PeriodicalIF":4.1000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genotypic Diversity and Molecular Basis of Fluconazole Resistance in Candida parapsilosis Clinical Isolates Collected Over 7 Years in a Tertiary-Care Hospital in North India.\",\"authors\":\"Vrinda Sharma, Sourav Das, Bram Spruijtenburg, Theun de Groot, Eelco Meijer, Harsimran Kaur, Shivaprakash M Rudramurthy, Anup Ghosh\",\"doi\":\"10.1111/myc.70062\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The recent rise in the global incidence of fluconazole resistance in C. parapsilosis has become a significant public health concern. Epidemiological studies suggest that fluconazole resistance in C. parapsilosis spreads through endemic clones. We, therefore, investigated the molecular epidemiology of fluconazole-resistant C. parapsilosis in our centre.</p><p><strong>Methods: </strong>C. parapsilosis isolates from 2016 through 2022 were investigated for antifungal susceptibility. Fluconazole-resistant isolates were analysed for ERG11 mutation using Sanger sequencing. Gene expression profiles of ERG11, CDR1 and MDR1 were assessed by real-time qPCR. The epidemiological relationship of resistant and susceptible isolates of C. parapsilosis was investigated using short tandem repeat typing. Additionally, biofilm production and cell wall ergosterol contents were also quantified and compared.</p><p><strong>Results: </strong>Among 572 C. parapsilosis isolates, 48 (8.4%) were resistant to fluconazole. Of 28 recoverable resistant isolates, 17.9% (5/28) were wild-type and 82.1% (23/28) harboured the following ERG11 mutations: Y132F (n = 3), K143R (n = 10) and K143R + R398I (10/28). Significant fold-changes were observed in ERG11 (p = 0.037) and MDR1 (p = 0.008) gene expressions in fluconazole resistant compared to susceptible isolates. Contrary to global reports, STR typing suggested a limited clonal transmission of resistant C. parapsilosis with multiple introductions of resistant isolates in our centre. On fluconazole exposure, ergosterol content significantly increased (p < 0.01) in resistant isolates, particularly in isolates harbouring ERG11<sup>K143R + R398I</sup> mutations. In contrast, fluconazole-susceptible isolates formed comparatively higher baseline biofilm (p < 0.05) than resistant isolates with ERG11<sup>K143R</sup> mutation.</p><p><strong>Conclusion: </strong>The current study underscores the need for continuous molecular surveillance and tailored therapeutic options for effective management of fluconazole resistance in C. parapsilosis.</p>\",\"PeriodicalId\":18797,\"journal\":{\"name\":\"Mycoses\",\"volume\":\"68 5\",\"pages\":\"e70062\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mycoses\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/myc.70062\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mycoses","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/myc.70062","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Genotypic Diversity and Molecular Basis of Fluconazole Resistance in Candida parapsilosis Clinical Isolates Collected Over 7 Years in a Tertiary-Care Hospital in North India.
Background: The recent rise in the global incidence of fluconazole resistance in C. parapsilosis has become a significant public health concern. Epidemiological studies suggest that fluconazole resistance in C. parapsilosis spreads through endemic clones. We, therefore, investigated the molecular epidemiology of fluconazole-resistant C. parapsilosis in our centre.
Methods: C. parapsilosis isolates from 2016 through 2022 were investigated for antifungal susceptibility. Fluconazole-resistant isolates were analysed for ERG11 mutation using Sanger sequencing. Gene expression profiles of ERG11, CDR1 and MDR1 were assessed by real-time qPCR. The epidemiological relationship of resistant and susceptible isolates of C. parapsilosis was investigated using short tandem repeat typing. Additionally, biofilm production and cell wall ergosterol contents were also quantified and compared.
Results: Among 572 C. parapsilosis isolates, 48 (8.4%) were resistant to fluconazole. Of 28 recoverable resistant isolates, 17.9% (5/28) were wild-type and 82.1% (23/28) harboured the following ERG11 mutations: Y132F (n = 3), K143R (n = 10) and K143R + R398I (10/28). Significant fold-changes were observed in ERG11 (p = 0.037) and MDR1 (p = 0.008) gene expressions in fluconazole resistant compared to susceptible isolates. Contrary to global reports, STR typing suggested a limited clonal transmission of resistant C. parapsilosis with multiple introductions of resistant isolates in our centre. On fluconazole exposure, ergosterol content significantly increased (p < 0.01) in resistant isolates, particularly in isolates harbouring ERG11K143R + R398I mutations. In contrast, fluconazole-susceptible isolates formed comparatively higher baseline biofilm (p < 0.05) than resistant isolates with ERG11K143R mutation.
Conclusion: The current study underscores the need for continuous molecular surveillance and tailored therapeutic options for effective management of fluconazole resistance in C. parapsilosis.
期刊介绍：
The journal Mycoses provides an international forum for original papers in English on the pathogenesis, diagnosis, therapy, prophylaxis, and epidemiology of fungal infectious diseases in humans as well as on the biology of pathogenic fungi.
Medical mycology as part of medical microbiology is advancing rapidly. Effective therapeutic strategies are already available in chemotherapy and are being further developed. Their application requires reliable laboratory diagnostic techniques, which, in turn, result from mycological basic research. Opportunistic mycoses vary greatly in their clinical and pathological symptoms, because the underlying disease of a patient at risk decisively determines their symptomatology and progress. The journal Mycoses is therefore of interest to scientists in fundamental mycological research, mycological laboratory diagnosticians and clinicians interested in fungal infections.
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