Title : Biotechnological exploration of phyto-drugs against MDR bacteria targeting DNA topoisomerase I and RNA polymerase
Alpha and Delta coronaviruses spread worldwide claiming >634000 lives and secondary multidrug-resistant infections were found a risk factor specifically in ICU patients containing carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecium and Klebsilla pneumoniae. MDR large (100-500kb) plasmids have acquired.>10 mdr genes (bla, aac, aph, aad, sul) and drug efflux genes (Tet, Acr, Mex) to inactivate antibiotics and the development of new antibacterial drugs are urgently needed. Plants secret anti-metabolites to retard growth of soil and water bacteria and are ideal sources of antibiotics. Six plants derived bacteriocidal organic extracts were selected testing 80 medicinal plants against MDR bacteria. The Cassia fistula bark saponin poly-Bromo-phenol compound (CU1) inhibited RNA polymerase from Escherichia coli as well as Mycobacterium tuberculosis as compared to rifampicin. Gel shift assays demonstrated that CU1 interferes at the open promoter complex formation step. Further, cultivated Suregada multiflora root extracts was found exceptionally active (18 fold than natural sources) against MDR bacteria. We purified the active principle NU2 by TLC and HPLC, and also confirmed by MASS, NMR and FT-IR. NU2 is a glycoside and inhibits unicellular parasites like Leishmania donovani, Trypanosoma brucei and Plasmodium falciparum. NU2 actively inhibited the DNA topoisomerase I and RNA polymerase to a lesser extent of Escherichia coli suggesting the modes of action. Scientists postulated that MDR infections might claim 10 million deaths as we would approach 2050. MDR void will increase due to few reasons: (1) mdr genes are accumulated in large conjugative plasmids with transposons and integrons; (2) the spread of mdr genes in Ganga river water bacteria is increasing at ~5%/year and (3) mdr genes creation facilitates to protect gut microbiota from repeated oral antibiotics use. Thus, Phyto-drug may be a solution to curve secondary MDR bacterial infections in coronavirus-infected patients.
Audience Take Away Notes:
- Phyto-drug research has prioritized by many Governments!
- Knowing the mechanism of inactivation of antibiotics by mdr enzymes!
- Some aspects of phyto-drug purification problems and chemical structure determination will be explained!
- To find a job today, you need to know in detail biochemistry and pharmacology!
- Leaders of poor countries should think for million of poor families as drug price sky rocketing!