AUTHOR=Yu Jingyi , Rao Lulin , Zhan Lingling , Zhou Yan , Guo Yinjuan , Wu Xiaocui , Song Zengqiang , Yu Fangyou 

TITLE=Antibiofilm Activity of Small-Molecule ZY-214-4 Against Staphylococcus aureus

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.618922

DOI=10.3389/fmicb.2021.618922

ISSN=1664-302X

ABSTRACT=<p><italic>Staphylococcus aureus</italic> is the most important pathogenic bacteria in humans. As the resistance of <italic>S. aureus</italic> to existing antibiotics is increasing, there is an urgent need for new anti-infective drugs. <italic>S. aureus</italic> biofilms cause persistent infections and resist complete eradication with antibiotic therapy. The present study investigated the inhibitory effect of the novel small-molecule ZY-214-4 (C<sub>1</sub><sub>9</sub>H<sub>1</sub><sub>1</sub>BrNO<sub>4</sub>) on <italic>S. aureus</italic> biofilm formation. At a subinhibitory concentration (4 μg/ml), ZY-214-4 had no effect on the growth of <italic>S. aureus</italic> strains and also showed no cytotoxicity in human normal bronchial epithelial cells (Bease-2B). The results of a semi-quantitative biofilm test showed that ZY-214-4 prevented <italic>S. aureus</italic> biofilm formation, which was confirmed by scanning electron microscopy and confocal laser scanning microscopy. ZY-214-4 significantly suppressed the production of polysaccharide intercellular adhesion and prevented cell aggregation, and also inhibited the mRNA expression of <italic>icaA</italic> and other biofilm-related genes (<italic>eno</italic>, <italic>clfA/B</italic>, <italic>fnbB</italic>, <italic>fib</italic>, <italic>ebpS</italic>, <italic>psm</italic>α, and <italic>psm</italic>β) in clinical <italic>S. aureus</italic> isolates. Thus, at a subinhibitory concentration, ZY-214-4 inhibits biofilm formation by preventing cell aggregation, highlighting its clinical potential for preventing or treating <italic>S. aureus</italic> infections.</p>