Drug resistance reversal potential of multifunctional thieno[3,2-c]pyran via potentiation of antibiotics in MDR P. aeruginosa.

We explored the antibacterial potential (alone and combination) against multidrug resistant (MDR) Pseudomonas aeruginosa isolates KG-P2 using synthesized thieno[3,2-c]pyran-2-ones in combination with different antibiotics. Out of 14 compounds, two compounds (3g and 3l) abridged the MIC of tetracycline (TET) by 16 folds. Compounds was killing the KG-P2 cells, in time dependent manner, lengthened post-antibiotic effect (PAE) of TET and found decreased the mutant prevention concentration (MPC) of TET. In ethidium bromide efflux experiment, two compounds repressed the drug transporter (efflux pumps) which is further supported by molecular docking of these compounds with efflux complex MexAB-OprM. In another study, these compounds inhibited the synthesis of biofilm.

Drug Resistance Reversal Potential of Nanoparticles/Nanocomposites via Antibiotic's Potentiation in Multi Drug Resistant P. aeruginosa.

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide-zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO-CS), a zinc oxide decorated graphene oxide-chitosan nanocomposite (GO-CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

Therapeutic Potential of Endophytic Compounds: A Special Reference to Drug Transporter Inhibitors.

From the discovery to the golden age of antibiotics (miracle), millions of lives have been saved. The era of negligence towards chemotherapeutic agents gave birth to drug resistance. Among all the regulators of drug resistance, drug transporters are considered to be the key regulators for multidrug resistance. These transporters are prevalent from prokaryotes to eukaryotes. Endophytes are one of the unexplored wealths of nature. Endophytes are a model mutualistic partner of plants. They are the reservoir of novel therapeutics. The present review deals with endophytes as novel drug resistance reversal agents by inhibiting the drug transporters across the genera. This review also focuses on drug transporters, and mutualistic chemical diversity, exploring drug transporter modulating potential of endophytes.