AUTHOR=Li Linhui , She Pengfei , Liu Shasha , Li Yimin , Li Zehao , Yang Yifan , Zhou Linying , Wu Yong 

TITLE=Identification of a small molecule 0390 as a potent antimicrobial agent to combat antibiotic-resistant Escherichia coli

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1078318

DOI=10.3389/fmicb.2022.1078318

ISSN=1664-302X

ABSTRACT=Antibiotic resistance has posed a serious challenge to global public health. With the increasing resistance emergence of E. coli and mortality caused by drug-resistant E. coli infections, it is urgent to develop novel antibiotics. By high-throughput screening assay, we found a bioactive molecule, 0390 (6056-0390), which demonstrated antimicrobial effects against E. coli. Moreover, 0390 showed significant synergistic antimicrobial effects in combination with SPR741, a polymyxin B derivative, against E. coli standard strain and extensively drug-resistant (XDR) clinical isolates, and the combination exhibited good safety property in vitro. In addition, we demonstrated that the combinational treatment of 0390 and SPR741 exhibited a considerable antibacterial activity in vivo, and no tissue damage or other toxicity was observed after the therapeutic dose treatment. Collectively, we have determined the in vitro and in vivo antimicrobial potential of 0390 alone or in combination with SPR741, which might be used as a treatment option for E. coli related infections.