Whole-Genome Sequence Analysis of Candida glabrata Isolates from a Patient with Persistent Fungemia and Determination of the Molecular Mechanisms of Multidrug Resistance

Autor: Ha Jin Lim, Min Ji Choi, Seung A. Byun, Eun Jeong Won, Joo Heon Park, Yong Jun Choi, Hyun-Jung Choi, Hyun-Woo Choi, Seung-Jung Kee, Soo Hyun Kim, Myung Geun Shin, Seung Yeob Lee, Mi-Na Kim, Jong Hee Shin
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Fungi, Vol 9, Iss 5, p 515 (2023)
Druh dokumentu: article
ISSN: 2309-608X
DOI: 10.3390/jof9050515
Popis: 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.
Databáze: Directory of Open Access Journals
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