AUTHOR=Xie Yunfeng , Wang Lei , Yang Yang , Zha Liang , Zhang Jiazhen , Rong Kuanrong , Tang Wenjian , Zhang Jing 

TITLE=Antibacterial and anti-biofilm activity of diarylureas against Enterococcus faecium by suppressing the gene expression of peptidoglycan hydrolases and adherence

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1071255

DOI=10.3389/fmicb.2022.1071255

ISSN=1664-302X

ABSTRACT=<p><italic>Enterococcus faecium</italic> (<italic>E. faecium</italic>) is a clinical multidrug-resistant pathogen causing life-threatening infection, which makes it important to discover antibacterial agents with novel scaffolds and unique mechanism. In this study, the diarylurea scaffold was found to have potent antibacterial effect on <italic>E. faecium</italic>. Diarylurea <bold>ZJ-2</bold> with benign drug-like property exhibited potent antibacterial and anti-biofilm activity through inhibiting the genes expression of NlpC/p60 hydrolase-secreted antigen A (<italic>sagA</italic>) and autolysins (<italic>atlA</italic>), down-regulating the expression of biofilm adherence related genes aggregation substance (<italic>agg</italic>), enterococcal surface protein (<italic>esp</italic>) against <italic>E. faecium</italic>. Moreover, <bold>ZJ-2</bold> can be docked into SagA to inhibit daughter cell separation. In a mouse model of abdominal infection, <bold>ZJ-2</bold> decreased the bacterial load and the level of IL-6 and TNF-α in a time-dependent manner. Overall, these findings indicated that diarylurea <bold>ZJ-2</bold> has the potential to be developed as a therapeutic agent to treat drug-resistant enterococci and biofilm-related infections.</p>