Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus.

Lulin Rao,Fangyou Yu,Jingyi Yu,Zengqiang Song,Yanlei Xu,Lingling Zhan,Yinjuan Guo,Xiaocui Wu,Huilin Zhao,Bingjie Wang,Yaoguang Sheng,Jiao Zhang,Xinyi Wang

doi:10.3389/fmicb.2021.770657

Abstract

The resistance of methicillin-resistant Staphylococcus aureus (MRSA) has augmented due to the abuse of antibiotics, bringing about difficulties in the treatment of infection especially with the formation of biofilm. Thus, it is essential to develop antimicrobials. Here we synthesized a novel small-molecule compound, which we termed SYG-180-2-2 (C21H16N2OSe), that had antibiofilm activity. The aim of this study was to demonstrate the antibiofilm effect of SYG-180-2-2 against clinical MRSA isolates at a subinhibitory concentration (4 μg/ml). In this study, it was showed that significant suppression in biofilm formation occurred with SYG-180-2-2 treatment, the inhibition ranged between 65.0 and 85.2%. Subsequently, confocal laser scanning microscopy and a bacterial biofilm metabolism activity assay further demonstrated that SYG-180-2-2 could suppress biofilm. Additionally, SYG-180-2-2 reduced bacterial adhesion and polysaccharide intercellular adhesin (PIA) production. It was found that the expression of icaA and other biofilm-related genes were downregulated as evaluated by RT-qPCR. At the same time, icaR and codY were upregulated when biofilms were treated with SYG-180-2-2. Based on the above results, we speculate that SYG-180-2-2 inhibits the formation of biofilm by affecting cell adhesion and the expression of genes related to PIA production. Above all, SYG-180-2-2 had no toxic effects on human normal alveolar epithelial cells BEAS-2B. Collectively, the small-molecule compound SYG-180-2-2 is a safe and effective antibacterial agent for inhibiting MRSA biofilm.

Highlights

Staphylococcus aureus is a pathogen that causes a variety of infections ranging from relatively benign to life-threatening infections including pneumonia, endocarditis, osteomyelitis, and sepsis (Cassat et al, 2007)
When methicillin-resistant Staphylococcus aureus (MRSA) strains acquire resistance to antibiotics and form robust biofilm, this leads to higher mortality, especially when they infect patients in the intensive care unit (ICU; Turner et al, 2019)
We synthesized a new small-molecule compound SYG-180-2-2 that possessed significant inhibitory activity against the biofilm of MRSA ranging from different types

Summary

Introduction

Staphylococcus aureus is a pathogen that causes a variety of infections ranging from relatively benign to life-threatening infections including pneumonia, endocarditis, osteomyelitis, and sepsis (Cassat et al, 2007). Due to the use of antibiotics, drug-resistant strains have increased rapidly, especially methicillin-resistant Staphylococcus aureus (MRSA) which is difficult to treat and has a SYG-180-2-2 Inhibits the Biofilm Formation high mortality rate (Mole, 2013). It was reported that some MRSA had even developed resistance to vancomycin which is the most effective antibiotic for the treatment of MRSA (Cong et al, 2020). Treatment with traditional antibiotics is ineffective to cope with the current severe drug resistance situation (Basnyat et al, 2015). It is urgent to develop new drugs that cannot only effectively inhibit biofilm formation and prevent bacterial mutations from developing drug resistance

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