MDR1 overexpression combined with ERG11 mutations induce high-level fluconazole resistance in Candida tropicalis clinical isolates
| العنوان: | MDR1 overexpression combined with ERG11 mutations induce high-level fluconazole resistance in Candida tropicalis clinical isolates |
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| المؤلفون: | Xiaojuan Wang, Hongbin Chen, Longyang Jin, Hui Wang, Zhuorui Cao, Yichen Wang, Qi Wang |
| المصدر: | BMC Infectious Diseases BMC Infectious Diseases, Vol 18, Iss 1, Pp 1-6 (2018) |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Antifungal Agents, Adolescent, 030106 microbiology, MDR1, Microbial Sensitivity Tests, lcsh:Infectious and parasitic diseases, Microbiology, Fungal Proteins, Candida tropicalis, Young Adult, 03 medical and health sciences, Medical microbiology, Cytochrome P-450 Enzyme System, Fluconazole resistance, Drug Resistance, Fungal, Gene expression, medicine, Humans, Missense mutation, lcsh:RC109-216, ATP Binding Cassette Transporter, Subfamily B, Member 1, Fluconazole, Aged, Aged, 80 and over, chemistry.chemical_classification, biology, Candidiasis, Middle Aged, biology.organism_classification, 030104 developmental biology, Infectious Diseases, Parasitology, chemistry, Mutation, Azole, Multilocus sequence typing, Female, Research Article, Multilocus Sequence Typing, medicine.drug |
| الوصف: | Background Marked increases in fluconazole resistance in Candida tropicalis have been recently reported. In this study, the molecular mechanisms behind fluconazole resistance were investigated. Methods Twenty-two C. tropicalis clinical isolates, including 12 fluconazole-resistant isolates and 10 fluconazole-susceptible isolates, were collected from a tertiary care teaching hospital in Beijing between 2013 and 2017. Antifungal susceptibility testing, multilocus sequence typing, ERG11 amplification and sequencing, quantitative real-time reverse transcription-polymerase chain reaction (ERG11, UPC2, MDR1, and CDR1), and clinical data collection were performed for all C. tropicalis isolates. Results Multilocus sequence typing revealed that the 10 fluconazole-susceptible isolates and 12 fluconazole-resistant isolates were divided into nine and seven diploid sequence types, respectively. Of the 12 patients with fluconazole-resistant isolates, six had been previously exposed to azole and four had a fatal outcome. Y132F and S154F amino acid substitutions in Erg11p were found in all fluconazole-resistant isolates except one. MDR1 gene overexpression was identified in fluconazole-resistant isolates. In particular, seven high-level fluconazole resistant isolates (minimum inhibitory concentration ≥ 128 mg/L) and three pan-azole resistant isolates were identified. CDR1, ERG11, and UPC2 gene expression levels in fluconazole-resistant isolates were not significantly different from the control isolates (P = 0.262, P = 0.598, P = 0.114, respectively). Conclusions This study provides evidence that the combination of MDR1 gene overexpression and ERG11 missense mutations is responsible for high-level fluconazole resistance and pan-azole resistance in C. tropicalis clinical isolates. To the best of our knowledge, this is the first study investigating the relationship between MDR1 gene overexpression and increased fluconazole resistance. |
| تدمد: | 1471-2334 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2551d332c8adacd17834b77a7f996b2dTest https://doi.org/10.1186/s12879-018-3082-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2551d332c8adacd17834b77a7f996b2d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712334 |
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