AUTHOR=Liang Tianyu , Chen Wei , Yang Xinyu , Wang Qiqi , Wan Zhe , Li Ruoyu , Liu Wei 

TITLE=The Elevated Endogenous Reactive Oxygen Species Contribute to the Sensitivity of the Amphotericin B-Resistant Isolate of Aspergillus flavus to Triazoles and Echinocandins

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.680749

DOI=10.3389/fmicb.2021.680749

ISSN=1664-302X

ABSTRACT=<p><italic>Aspergillus flavus</italic> has been frequently reported as the second cause of invasive aspergillosis (IA), as well as the leading cause in certain tropical countries. Amphotericin B (AMB) is a clinically important therapy option for a range of invasive fungal infections including invasive aspergillosis, and <italic>in vitro</italic> resistance to AMB was associated with poor outcomes in IA patients treated with AMB. Compared with the AMB-susceptible isolates of <italic>A. terreus</italic>, the AMB-resistant isolates of <italic>A. terreus</italic> showed a lower level of AMB-induced endogenous reactive oxygen species (ROS), which was an important cause of AMB resistance. In this study, we obtained one AMB-resistant isolate of <italic>A. flavus</italic>, with an AMB MIC of 32 μg/mL, which was sensitive to triazoles and echinocandins. This isolate presented elevated endogenous ROS levels, which strongly suggested that no contribution of decreased AMB-induced endogenous ROS for AMB-resistance, opposite to those observed in <italic>A. terreus</italic>. Further, we confirmed that the elevated endogenous ROS contributed to the sensitivity of the AMB-resistant <italic>A. flavus</italic> isolate to triazoles and echinocandins. Further investigation is needed to elucidate the causes of elevated endogenous ROS and the resistance mechanism to AMB in <italic>A. flavus</italic>.</p>