Title : Indian medicinal phytoextracts to tackle multi-drug resistant bacterial infections targeting RNA polymerase and DNA topoisomerase
Abstract:
Gradual increase of multidrug resistant infections is a threat to the human race as MDR plasmids have acquired.>10 mdr and drug efflux genes to inactivate antibiotics. Plants secret anti-metabolites to retard growth of soil and water bacteria and are ideal source of antibiotics. Six plants derived bacteriocidal organic extracts were selected testing 80 medicinal plants against MDR bacteria. A Cassia fistula saponin bromo-polyphenol compound (CU1) ran fast on TLC and purified on HPLC C18 column at 3min. CU1 is three times less active than rifampicin in Agar-hole assay. CU1 inhibited transcription from Escherichia coli as well as Mycobacterium tuberculosis RNA Polymerases. Gel shift assays demonstrated that CU1 interferes at the open promoter complex formation step. Phytochemicals are unstable and we thought three possible remedies: (a) search for more active and stable extracts, (b) cultivation of plant in big clay pot keeping in the roof top located in cities, and (c) plant tissue culture. A single tree of Suregada multiflora was grown five years in roof top at Kolkata and its root extracts was found exceptionally active (18 fold than natural sources) against MDR bacteria. Further, in MS tissue culture media with plant hormones IAA and 6-BA (2.5µg/ml), over-produced active principles further 2.8fold. We purified the active principle NU2 by TLC and HPLC, and also confirmed by MASS, NMR and FT-IR. NU2 phytochemical also inhibited some parasites like Leishmania donovani, Trypanosoma brucei and Plasmodium falciparum. NU-2 actively inhibited the DNA topoisomerase I and RNA polymerase of Escherichia coli suggesting the modes of action. Thus, cities of poor nations with population burden should cultivate medicinal plants in small garden or roof top in a similar way for superbug treatment where common antibiotic therapy fail. This message is urgent and universal as scientists projected that MDR spreading may claim 10 million people in the Asian countries as we would approach 2050. We think antibiotic void will continue due to few reasons:
(1) mdr genes are accumulated in large conjugative plasmids as well as chromosome islands with many transposons.
(2) the spread of mdr genes in plasmids is increasing at 5%/year.
(3) a critical message has generated to protect symbiosis relation between gut bacteria and human facilitating efficient mdr genes creation to protect gut microbiota from antibiotics as well as helping vitamin synthesis for human metabolosome.
