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

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.

The Association between Biofilm Formation and Antimicrobial Resistance with Possible Ingenious Bio-Remedial Approaches

“…Small molecules, such as 5-fluorouracil, which targets quorum sensing, and synthetic molecules, such as terrain, which targets both quorum sensing as well as c-di-GMP, can be considered for anti-biofilm strategies. Novel molecules, such as SYG-180-2-2, with the ability to reduce the bacterial adhesion and polysaccharide intercellular adhesin (PIA) in methicillin-resistant Staphylococcus aureus should be seen as potential antibacterial agents [ 194 , 195 ]. Although the exact anti-biofilm mechanism of a few small molecules or drug candidates such as TAGE and CAGE are not entirely understood, their effectiveness against biofilm-causing microorganisms can still pave the road to combat biofilm-led AMR.…”

Small-molecule compound SYG-180-2-2 attenuates Staphylococcus aureus virulence by inhibiting hemolysin and staphyloxanthin production

“…SYG-180-2-2 was synthesized by the School of Pharmacy, Wenzhou Medical University ( Sheng et al., 2021 ). The details of the molecular structure, synthesis process and characterization of SYG-180-2-2 were shown in our previous study ( Rao et al., 2021 ).…”

“…The broth microdilution method based on CLSI guidelines was used to determine the minimal inhibitory concentration (MIC) ( CLSI, 2019 ). Specific methods for MIC values and growth curves of SYG-180-2-2 against S. aureus strains were described in our previous study ( Rao et al., 2021 ).…”

“…In our knowledge, there is also no study on novel anti-virulence drugs combined with 3-selenylindole and the amido group. Following our discovery of anti-biofilm ability of SYG-180-2-2 ( Rao et al., 2021 ), we are interested in exploring the anti-virulence of this new compound.…”

Targeted Anti-Biofilm Therapy: Dissecting Targets in the Biofilm Life Cycle

“…Research by Heras et al showed that blocking the super adhesion protein ( UpaB ) of bacteria could effectively inhibit bacterial colonization in the host [ 71 ]. Zhan et al synthesized an indole derivative of selenium-containing (SYG-180-2-2, C 21 H 16 N 2 OSe), which could inhibit biofilm by downregulating icaA and icaD and upregulating icaR and coY , thereby affecting PIA ( ica : intercellular adhesin) [ 72 ]. Ravi et al demonstrated that 2-hydroxy-4-methoxyben- zaldehyde (HMB, natural product of Hemidesmus indicus ) could target the initial cell adhesion of Staphylococcus epidermidis ( S. epidermidis ) ( Figure 2 a) [ 73 ].…”