Bacterial multidrug resistance (MDR) is a significant issue in the medical community. Gram-negative bacteria (GNB) exhibit higher rates of MDR, partly due to the impermeability of the GNB double membrane cell envelope, which limits the internal accumulation of antibiotic agents. In Escherichia coli, a GNB, the genes accA and accD, produce the AccA and AccD subunits of the acetyl-CoA carboxylase transferase enzyme that is essential for catalyzing fatty acid synthesis (FAS). FAS produces phospholipids that comprise the double membrane required for forming viable and antibiotic resistant GNB. Therefore, FAS affects the composition of GNB cell membranes and can alter antibiotic susceptibility. However, the association between fatty acid metabolism, virulence, and antibiotic uptake requires further elucidation. For this reason, the current study investigated the link between fatty acid metabolism, virulence, and antibiotic susceptibility by disrupting FAS in E. coli via antisense RNA (asRNA) inhibition of accA. Suppression of FAS through asRNA inhibition of accA, downregulated luxS, which is a vital virulence factor for mediating pathogenic bacterial quorum sense (QS) signaling and decreased antibiotic resistance in E. coli. The results of this study confirm that accA is a potent target for developing novel antimicrobial gene therapies.
Antibiotic resistance; Antibiotics; Carboxylase enzymes; Autoinducers; Quorum sense; Antisense RNA; Fatty acid synthesis