RT Journal Article SR Electronic T1 Antisense inhibition of accA suppressed luxS expression that is essential for quorum sense signaling, biofilm formation, and virulence JF bioRxiv FD Cold Spring Harbor Laboratory SP 747980 DO 10.1101/747980 A1 Tatiana Hillman YR 2020 UL http://biorxiv.org/content/early/2020/09/08/747980.abstract AB 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 StatementThe authors have declared no competing interest.