RNAi for silencing drug resistance in microbes toward development of nanoantibiotics

Multidrug-resistant microorganisms (MDRMOs) are progressively becoming an unavoidable challenge to worldwide health. Conventional antibiotics pressure resulted in increased bacterial efflux pumps lessening drug concentrations, up-regulated enzymes modifying/inactivating antibiotic compounds, or elevated mutations in the drug target site reducing antibiotic potency. Therefore, effective therapy for combating the emerging rate of MDRMOs requires innovative, combinatory strategies of generating conventional antimicrobial effects and simultaneously silencing drug-resistance processes in microbes. RNA interference (RNAi) is a revolutionary technology with high potential for obtaining synergistic therapies by knocking down antagonistic pathways with genomic specificity at a translational level. However, employing RNAi in antimicrobial therapy, particularly treating drug-resistant infections, has not received a great deal of attention. This paper briefly reviews key drug-resistance mechanisms in microbes, discusses the possibility of sensitizing MDRMOs to conventional antimicrobial therapy by combining it with RNAi, and introduces novel nano-scale formulation for efficient administration of such therapy (nanoantibiotics). The combined, synergistic antimicrobial therapy using antibiotics and RNAi may shed light when the current pipeline for new antibiotics is outrun by emergence of MDRMOs.