Numerous studies have shown that bacteria quantify their density and collectively carry out a certain response with a communication mechanism known as quorum sensing. Biofilms are a type of virulence factor that forms once a bacterial quorum is reached within the host, preventing the host’s immune system from detecting and ultimately eradicating these pathogenic bacteria. Efflux pumps may also be involved in biofilm production. These pumps are transport proteins that are responsible for the extrusion of various substances, including toxins, quorum sensing molecules, and biofilm components. The increased activity of efflux pumps has allowed antibiotic-resistant bacteria to increase their survival rates. This study tests certain drugs that were designed to resemble quorum sensing signaling molecules to inhibit biofilm formation. Since these drugs also have structural homology with known Nor-A efflux pump inhibitors (EPI) in S. aureus, we tested their activity on this pump. Fourteen of our previously synthesized drugs share this structural homology, with five of them revealing significant biofilm reduction in SA-1199 (wildtype) and SA-1199B (Nor-A overexpressor) but not in SA-K1758 (Nor-A knockout). This indicates that the drugs function in targeting the Nor-A pump rather than as competitive inhibitors at the receptor sites of the S. aureus. The conjugated aromatic ring with alternating electron-withdrawing and donating groups on the ortho and para positions appear to affect the inhibitory characteristics of these drugs. Developing a cocktail of drugs that curtail quorum sensing and inhibit efflux pump activity can maximize biofilm inhibition in S. aureus.

Novel lead compounds demonstrating anti-biofilm properties in <i>Staphylococcus aureus</i> may act as Nor-A efflux pump inhibitors.

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Novel lead compounds demonstrating anti-biofilm properties in Staphylococcus aureus may act as Nor-A efflux pump inhibitors.