Heterogeneous Phyto-Antibiotics and Other Future Therapeutics Against Multi-Drug Resistant Bacteria

Abstract

Phage therapy, enzybiotics, gene medicine and nanodrug-carriers are most vital components of modern research against multidrug-resistant bacteria. Genome evolution occurs due to environmental toxicities of various types where soil bacteria are in symbiosis with plant world who secret anti-metabolites against soil bacteria. Gut microbiome secrete vitamins required for our body where as intestinal cells synthesis interleukins and cytokines for symbiotic control of intestinal bacteria. Before the discovery of antibiotic in 1928, peoples trusted plant derived remedies against variety of illness described in Indian Sanskrit books like Charaka Samhita, Sasruta Samhita and Atharva Veda. AMR disease occurred due to repeated but uncontrolled use of antibiotics affecting gut microbiome who acquired many mdr genes in plasmids. We estimated that 40% of all river and sea water borne bacteria were ampicillin and to lesser extent tetracycline, azithromycin, ciprofloxacin and streptomycin resistant. Where as <1% were multidrug-resistant and ~0.002% Enterobacteriaceae were meropenem, linezolid or amikacin resistant. MDR genes like amp, neo, tet, aac, cat, aph, aad, arr3, sul1, dhfr, inh, acrAB, mexAB, macAB and mtrCD were amplified with millions mutated isomers increasing all drugs MIC. We studied Indian medicinal plants and spices to get valuable cheap drugs where modified agriculture and/or tissue culture increased the drug concentration. We showed that MDR bacteria were sensitive to organic extract of Suregada multiflora roots, Cassia fistula bark, Jatropha gossypifolia roots as well as Indian spices Labanga and Derchini (MDR-Cure). TLC and HPLC purification as well as UV-VIS, MASS, NMR, FT-IR and XRD-Powder gave many distinct signatures of pure chemicals that also inhibited multidrug-resistant bacteria. Biological targets of 12 chemicals are under investigation targeting DNA Topoisomerase I, DNA Polymerase and RNA Polymerase of Escherichia coli. Indian Government has started Herbal Mission, Ganga Mission and various Plantation Programmes to curve MDR pathogenesis.

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

“…We slogan "save plants and use as medicine" to save millions of peoples those are dragged into nasty poverty line each year due to high cost of antibiotics. Of course, drug void will increase with time as 20-60 transposable elements and rDNA recombinases were assembled in plasmids making easy new mdr gene creation [20,47,48]. In summary, we proved that mdr genes are not Citation: Poria immediate threat.…”

“…However, such dream could not last long as more potent penicillinases called, oxacillinases (blaOXA), cefotaximases (blaCTX-M), carbapenemases (blaKPC) were appeared in bacterial plasmids between 1940-1990 increasing drug resistance and antibiotic failure [17][18][19][20].…”

<strong>Coronavirus ORF1ab Polyprotein Associated Nsp16 Protein is a RlmE Methyltransferase and May Methylate 21S Mitochondrial rRNA of Most Mells Inhibiting Protein Synthesis</strong>

“…Targeting cellular autophagy may be one such application to control covid-19 mRNA genome release into cell cytoplasm (Prentice et al 2004). Natural products have shown to regulate microbes and became good drugs controlling superbug bacteria, malaria and cancer (Chakraborty, 2019;Newman & Cragg , 2012;. The 7a protein of Coronavirus has shown to induce apoptosis by caspase-dependent pathways and thus antibody against 7a protein may be a drug against viral pathogenesis (Tan et al 2004).…”

“…The primers designed (figure-8) using Coronavirus rlmE gene sequence may be used for diagnosis and therapeutic discovery in the future. Heterogeneous phyto-antibiotics, gene therapy, anti-sense and ribozyme technology and nano-drug carriers may be future medicine against Covid-19 (Cao et al 2015;Chakraborty, 2019).…”

An Abundant New Saponin-Polybromophenol Antibiotic (CU1) fromCassia fistulaBark Against Multi-Drug Resistant Bacteria Targeting RNA Polymerase

“…Few dozens mdr genes were isolated and sequenced but million mutated isolates with potential higher drug inactivating capabilities were documented in human infections caused by Salmonella, Pseudomonas, Acinetobacter, Klebsiella, Bacillus and Escherichia species [4][5][6][7]. Importantly, small Rplasmids with 1-3 mdr genes have combined with F'-conjugative plasmid (62.5kb) giving more space to multiple (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) mdr genes as well as drug-efflux genes and many recombinases and IS-elements. Such bacteria can donate the mdr genes to other environmental bacteria by conjugation where we found 45% ampicillin resistance bacteria in Ganga River water and Digha sea water but reported clinical isolates were >95% ampicillin resistant [8].…”