| Autor: |
Lim HJ; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Choi MJ; Microbiological Analysis Team, Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea., Byun SA; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Won EJ; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea.; Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Park JH; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Choi YJ; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Choi HJ; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Choi HW; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Kee SJ; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Kim SH; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Shin MG; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea., Lee SY; Department of Laboratory Medicine, Jeonbuk National University Medical School and Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea.; Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea., Kim MN; Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Shin JH; Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju 61469, Republic of Korea. |
| Abstrakt: |
Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced using a Nextera DNA Flex Kit (Illumina) and the MiseqDx (Illumina) instrument. All isolates harbored the same Msh2p substitution, V239L, associated with multilocus sequence type 7 and a Pdr1p substitution, L825P, that caused azole resistance. Of six isolates with increased AMB MICs (≥2 mg/L), three harboring the Erg6p A158fs mutation had AMB MICs ≥ 8 mg/L, and three harboring the Erg6p R314K, Erg3p G236D, or Erg3p F226fs mutation had AMB MICs of 2-3 mg/L. Four isolates harboring the Erg6p A158fs or R314K mutation had fluconazole MICs of 4-8 mg/L while the remaining six had fluconazole MICs ≥ 256 mg/L. Two isolates with micafungin MICs > 8 mg/L harbored Fks2p (I661_L662insF) and Fks1p (C499fs) mutations, while six isolates with micafungin MICs of 0.25-2 mg/L harbored an Fks2p K1357E substitution. Using WGS, we detected novel mechanisms of AMB and echinocandin resistance; we explored mechanisms that may explain the complex relationship between AMB and azole resistance. |
