Role of Small Volatile Signaling Molecules in the Regulation of Bacterial Antibiotic Resistance and Quorum Sensing Systems

Many chemical processes in the cells and microorganisms in our body and environmental niches produce and release thousands of diffusible small molecular weight metabolites and volatile organic compounds (VOCs). Their chemical classes include hydrocarbons, esters, alcohols, ketones, terpenes, acids, nitrogen, and sulfur-containing compounds. Specific VOCs or their signatures were found to control the growth and antibiotic resistance of human commensal and pathogenic strains, including Staphylococcus aureus, Streptococus pneumoniae, Klebisiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Clostridium difficile. Gram-positive and -negative bacteria synchronize their population density and biochemical processes through a collective cell-to-cell communication system named quorum sensing (QS). Various bacterial QS operons that control the production, detection, and extracellular release of acylated homoserine lactones (AHLs), Furanosyl borate diester, peptides, oligopeptides, and small volatile compounds were discovered recently. Here we first outline the host and microorganism biochemical and metabolic pathways for production of VOCs and antibiotic resistance mechanisms. Next, we introduce QS mechanisms and provide future perspectives on potential roles of VOCs, AHLs, peptides, oligopeptides, and quorum quenching (QQ) inhibitors in controlling bacterial infection and antimicrobial-induced resistance.