Venkateswarlu K, Taylor M, Manning N J, Rinaldi M G, Kelly S L
Department of Molecular Biology and Biotechnology, The University of Sheffield, United Kingdom.
Antimicrob Agents Chemother. 1997 Apr;41(4):748-51. doi: 10.1128/AAC.41.4.748.
Eleven isolates of Cryptococcus neoformans were investigated to determine the biochemical basis of their tolerance to fluconazole. The MICs of fluconazole for three isolates with low-level resistance were 3- to 6-fold higher than those for sensitive isolates, while the MICs for four isolates with high-level resistance were 100- to 200-fold higher than those for sensitive isolates. The level of ergosterol present in the isolates varied, and those which had relatively low levels of ergosterol were resistant to amphotericin B. Changes in the affinity of the target enzyme (sterol 14alpha-demethylase) and decreases in the cellular content of fluconazole seemed to be responsible for the resistance in isolates with low-level and high-level resistance, respectively.
对11株新型隐球菌分离株进行了研究,以确定其对氟康唑耐受性的生化基础。三株低水平耐药分离株的氟康唑最低抑菌浓度(MIC)比敏感分离株高3至6倍,而四株高水平耐药分离株的MIC比敏感分离株高100至200倍。分离株中麦角固醇的含量各不相同,麦角固醇含量相对较低的分离株对两性霉素B耐药。靶酶(甾醇14α-脱甲基酶)亲和力的变化和氟康唑细胞内含量的降低似乎分别是低水平和高水平耐药分离株耐药的原因。