Mechanism of multi-resistant bacterial pathogenesis: MDR genes are not so deadly unless plasmid-mediated toxin, virulence and regulatory genes are activated

Kousik Poria, Shampa Bhatta, Sanatan Das, Madhumita Dey, Chandan Halder, Sankalita Datta and Asit Kumar Chakraborty*

Mdr genes in association with many drug efflux and metal efflux genes are creating pathogenesis due to antibiotic void. However, most dangerous step occurred when R-plasmids and integrons (~2-9kb) were combined with F’-conjugative plasmid (62.5kb) creating large MDR conjugative plasmids that easily donated 6-15 mdr genes to gut microbiota as well as environmental bacteria. Notably, 2-4x1012 human gut microbiota are very valuable in our body for vitamins synthesis and coenzymes perform >30,000 enzymatic reactions of human and animal metabolosome. It seems mdr gene creation is becoming more easy day by day as plasmids have acquired many gene creation genes like recombinases, DNA polymerases, DNA topoisomerases, integrases and transposases. In truth, antibiotics pressure was so instrumental that 25-40% bacteria of Ganga River and Bay of Bengal water were ampicillin and tetracycline resistant and more than 20 class of β-lactamases and drug transporters were generated in MDR plasmids with millions of mutated isomers increasing drugs MIC. When isolated superbugs were injected into male Wister rats, no detectable toxicity was observed up to 3-6 months follow up. We propose that mdr genes are not so injurious unless toxins and virulence genes with signalling and transcriptional regulators are activated in plasmids. Likely, mdr genes are protected by a tight symbiosis involving bio-film formation in the gut for vitamin synthesis. We also found a gradual increase of larger plasmids in the GenBank database with multiple mdr genes, drug efflux genes, regulatory genes, vitamin synthesizing genes and metal resistant genes as well as abundant (20-40) transposons and IS-elements. WHO, UNDP and CDC have suggested to develop alternate to antibiotics like phage therapy, gene therapy and nanotechnology based toxic drug delivery. We are actively using heterogeneous phyto-antibiotics from Suregada multiflora (root), Cassia fistula (bark) and Trapa bispinosa (fruit peel) targeting superbug central dogma machinery with success.

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Published on: Apr 4, 2020 Pages: 8-19

Full Text PDF Full Text HTML DOI: 10.17352/ojb.000013
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