Nagi Minoru, Tanabe Koichi, Tanaka Kazuko, Ueno Keigo, Nakayama Hironobu, Ishikawa Jun, Abe Masahiro, Yamagoe Satoshi, Umeyama Takashi, Nakamura Shigeki, Sugai Motoyuki, Hazen Kevin C, Miyazaki Yoshitsugu
Department of Fungal Infection, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
JAC Antimicrob Resist. 2022 Mar 7;4(1):dlac018. doi: 10.1093/jacamr/dlac018. eCollection 2022 Mar.
is an emerging fungal pathogen in immune-compromised hosts. Previously undetected isolates were successfully recovered from clinical specimens by adding sterols to the growth medium. The clinical isolates are unable to synthesize ergosterol but can take up exogenous sterols under aerobic conditions.
This study characterizes the sterol-auxotrophic strains, examines the mutation(s) in sterol synthesis genes, characterizes the drug susceptibility and evaluates the virulence in a mouse infection model.
Drug susceptibility of the strains was evaluated in a sterol-supplemented medium. The coding sequences of the sterol synthesis genes were analysed in six sterol-auxotrophic strains of . The fungal burden of mice infected with strain was determined.
The sterol-auxotrophic strains showed high-level resistance to both azoles and amphotericin B when sterols were supplied in the test medium. Additionally, the strains harbour missense mutations in either or . Significant differences in fungal burden were not observed between the sterol-auxotrophic strain and the sterol-competent strain with the mice infection models.
The sterol-auxotrophic strain investigated in this study seemed to maintain intact virulence, probably due to the supply of exogenous sterols from host organ(s). This suggests that exogenous sterol uptake develops antifungal resistance during infection.
是免疫功能低下宿主中一种新出现的真菌病原体。通过在生长培养基中添加甾醇，先前未检测到的分离株已成功从临床标本中分离出来。临床分离株无法合成麦角甾醇，但在有氧条件下可以摄取外源性甾醇。
本研究对甾醇营养缺陷型菌株进行特征分析，检测甾醇合成基因中的突变，确定药物敏感性，并在小鼠感染模型中评估其毒力。
在添加甾醇的培养基中评估菌株的药物敏感性。分析了6株甾醇营养缺陷型菌株中甾醇合成基因的编码序列。测定感染菌株的小鼠的真菌负荷。
当在测试培养基中提供甾醇时，甾醇营养缺陷型菌株对唑类和两性霉素B均表现出高水平耐药。此外，这些菌株在或中存在错义突变。在小鼠感染模型中，甾醇营养缺陷型菌株和甾醇合成能力正常的菌株之间未观察到真菌负荷的显著差异。
本研究中所研究的甾醇营养缺陷型菌株似乎保持了完整的毒力，这可能是由于宿主器官提供了外源性甾醇。这表明在感染过程中摄取外源性甾醇会产生抗真菌耐药性。
