Small Drug Molecules that Resemble Bacterial Signaling Molecules Act as Competitive Inhibitors with Intramolecular Communication Signals at Bacterial Receptor Sites

Abstract

Contemporary studies have discovered that bacteria are multilingual, having both intraspecies and interspecies communication capabilities. Through quorum sensing, bacteria quantify their density and unanimously agree on carrying out a certain response (Bassler 2009). Biofilms are virulence factors that form once a bacterial quorum is reached within the host, preventing the host�s immune system from detecting and ultimately eradicating these pathogenic bacteria (Hensel 2020). This study tests certain drugs that could potentially prevent successful bacterial communication, as biofilms impact various industries including medicine, dentistry, and agriculture for years (Urry et al. 2017). The Crystal Violet assays reveal that Glu-8, Gly-8, Gly-30, and Sar-6 drugs had 84.84, 71.48, 62.48, and 58.23 average percent inhibitions in B. subtilis respectively. Glu-8 had 37.20 average percent biofilm inhibition in S. mutans, while Glu-8 in S. aureus was a major biofilm accelerator in the second trial (-31.63%) and inhibitor in the first (29.33%). None of the drugs demonstrated biofilm inhibition in the Congo Red assays. Similarly, none of the tested drugs demonstrated any bacteriostatic effects when added to their bacterial cultures in the Disk Diffusion plates. Likewise, none of the drugs in the Use-Dilution plates were bactericidal. Although Glu-8 in B. subtilis and S. mutans and Sar-6 in B. subtilis were consistent biofilm inhibitors, further Crystal Violet trials are necessary to determine their biofilm inhibition ranges, and to determine whether Glu-8 is an inhibitor or accelerator in S. aureus. Accordingly, the combination of Glycine (Gly) and o-Bromobenzoic acid (bromine attached to the benzene functional group) resulted in an effective biofilm inhibitor without any bacteriostatic or bactericidal effects. Therefore, Glu-69 and Gly-69 should be tested in the future to analyze the effect of two bromines on a benzene ring. By doing so, certain functional groups could be characterized by their success in mimicking bacterial signals and ultimately inhibiting intraspecies communication. The aim is also to test Gly-10 to confirm that bromine attached to a benzene ring in the drug is what causes successful mimicking of endogenous intraspecific ligands, and not the bromine alone.