AUTHOR=Lin Yishuai , Zhang Ying , Liu Shixing , Ye Dandan , Chen Liqiong , Huang Na , Zeng Weiliang , Liao Wenli , Zhan Yizhou , Zhou Tieli , Cao Jianming 

TITLE=Quercetin Rejuvenates Sensitization of Colistin-Resistant Escherichia coli and Klebsiella Pneumoniae Clinical Isolates to Colistin

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.795150

DOI=10.3389/fchem.2021.795150

ISSN=2296-2646

ABSTRACT=<p>Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant <italic>Escherichia coli</italic> (<italic>E. coli</italic>) and <italic>Klebsiella Pneumoniae</italic> (<italic>K. pneumoniae</italic>). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant <italic>E. coli</italic> and <italic>K. pneumoniae</italic>, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of <italic>mcr-1</italic> and <italic>mgrB</italic> that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant <italic>E. coli</italic> and <italic>K. pneumoniae</italic> both <italic>in vitro</italic> and <italic>in vivo</italic>. Therefore, our results may provide an efficient alternative pathway against colistin-resistant <italic>E. coli</italic> and <italic>K. pneumoniae</italic> infections.</p>