Abstract
Staphylococcus aureus is the most important pathogenic bacteria in humans. As the resistance of S. aureus to existing antibiotics is increasing, there is an urgent need for new anti-infective drugs. S. aureus 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 (C19H11BrNO4) on S. aureus biofilm formation. At a subinhibitory concentration (4 μg/ml), ZY-214-4 had no effect on the growth of S. aureus 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 S. aureus 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 icaA and other biofilm-related genes (eno, clfA/B, fnbB, fib, ebpS, psmα, and psmβ) in clinical S. aureus isolates. Thus, at a subinhibitory concentration, ZY-214-4 inhibits biofilm formation by preventing cell aggregation, highlighting its clinical potential for preventing or treating S. aureus infections.
Highlights
Biofilm formation presents a major challenge for the eradication of chronic S. aureus infections (Craft et al, 2019)
We investigated the effect of a subinhibitory concentration of the small-molecule ZY-214-4 on S. aureus biofilm formation in order to assess the clinical potential of ZY214-4 for preventing and treating persistent S. aureus infection
We generated growth curves for cells treated with various concentrations of ZY-214-4 and found that at the subinhibitory concentration of 4 μg/ml, the number of cells in the late logarithmic growth phase was consistent across strains (Figure 2)
Summary
“An antimicrobial agent” is defined as a chemical produced by microbes that can inhibit the growth of and even destroy bacteria and other microorganisms (Waksman, 1947). There is a need for new compounds that can block the production of pathogenic factors and biofilm formation by S. aureus at sub-bacterial concentrations. The process of biofilm formation includes initial adhesion, proliferation, maturation, and diffusion (Boles and Horswill, 2011), with polysaccharide intercellular adhesin (PIA) providing a stable hydrated matrix that holds cells together in a threedimensional (3D) structure (Atshan et al, 2012). The recognition of Microbial Surface Components Recognize Adhesive Matrix Molecules (MSCRAMMs) determines the primary stage of S. aureus biofilm development, that is, the initial attachment to the host cell surface. These MSCRAMMs includes elastin binding protein (ebpS), laminin-(eno), fibronectin binding protein (fnbA and fnbB), fibrinogen binding protein (fib) and aggregation factor (clfA and clfB).
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