With ongoing concerns about antimicrobial resistance, researchers continue to explore alternative options to antimicrobial drugs (AMDs). In September, the Gluck Equine Research Center hosted a presentation by PhD student Bibek Lamichhane about quorum sensing inhibitors as novel antibiotic alternatives for controlling Salmonella infections.
Effects of Quorum Sensing on Bacterial Populations
Quorum sensing (QS) is important to bacterial populations for cell-to-cell communications. As Escobar-Muciño et al. described in a 2022 journal article, QS inhibitors are regulated by synthesis release and uptake of special signal molecules called autoinducers (AI), which respond to changes in bacterial population density. A change in the concentration of AI molecules in the environment collectively alters gene expression patterns within a bacterial population to promote bacterial adaptation important for survival.
Gram-negative and Gram-positive organisms produce different autoinducers. Because Salmonella spp. Is often resistant to drugs, alternatives to AMDs are helpful in controlling outbreaks. Salmonella spp. produces autoinducer-2, which modulates various cellular processes involved in coordination of collective behavior, such as regulation of virulence factors, colonization, bacterial luminescence, sporulation, motility, toxin production, biofilm formation, and drug resistance.
Quorum Sensing Inhibitors
According to Lamichhane, “small molecules” are referred to as QS inhibitors. While small in size, they are stable and obtained either from chemical synthesis or as a natural compound. With a molecular weight of 200 microns, they penetrate cells easily, allowing them to target intracellular processes to inhibit or degrade AI molecules, biosynthesis, or receptors. In his study, Lamichhane examined the best small molecules effective in vitro against S. typhimurium. All 10 small molecules tested demonstrated 100% inhibition and better efficacy compared to benchmark compounds. All have high efficacy at a low dose (5 uM) concentration and effectively inhibit biofilm formation. The small molecules further downregulate QS-associated genes.
Quorum sensing inhibitors achieve an antimicrobial effect without generating microbial resistance. They inhibit virulence rather than bacterial growth, minimizing resistant gene generation. QS inhibitors might act synergistically with some conventional antibiotics to reduce biofilm formation while increasing bacterial susceptibility. It is possible that certain bacteria might grow resistant to QS inhibitors. Future research should highlight more clinical applications for this modality in both human and equine medicine.
Reference
Escobar-Muciño E, Arenas-Hernández MMP, Luna-Guevara ML. Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella. Microorganisms 2022, 10, 884. https://doi.org/10.3390/microorganisms10050884
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