ABSTRACT
Bacterial multiple drug resistance (MDR) is a major issue for the medical community. Gram-negative bacteria (GNB) exhibit higher rates of multidrug resistance. Gram-negative bacteria are more resistant to multiple antibiotics. The double membrane contains an outer membrane with a lipid bilayer of lipopolysaccharides (LPS) and an inner cytoplasmic membrane (IM). Gram-negative bacteria limit hydrophobic particle influx via OM and hydrophilic molecule import through the IM. The translation of accA produces the AccA subunits of acetyl-CoA carboxylase transferase (ACCase-CT) enzymes required for catalyzing the output of fatty acids (FA) and phospholipids of the IM. Inhibiting accA can eliminate the AccA subunits of the ACCase-CT enzyme, which then block and decrease FAS. A deletion of luxS, in which LuxS develops virulent biofilm via the LuxS/AI-2 QS system, also reduces the output of FAs. Because accA and luxS both affect the output of FAs, a possible link between accA and luxS was examined by antisense RNA inhibition of accA and then applying real-time PCR (qPCR) for absolute quantification of luxS. The gene accA was inhibited with antisense RNA and produced a qPCR product of 63 ng/μL. The inhibition of accA suppressed the expression of luxS to 199 qPCR products versus 1×106 gene copies for the control. Bacterial cells that expressed antisense inhibition of accA also displayed a higher level of antibiotic susceptibility. Utilizing accA and luxS inhibitors to restrain FAS may provide potential targets for developing novel antimicrobial gene therapies for MDR-GNB.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Included more citations for the gram-negative membrane structure.