Mechanisms of Amr and Superbug Spread

...

Bacteria moved mdr genes into chromosome for better survival

Bacteria also made safe guard by combining mdr genes into its chromosome and few bacteria like Staphylococus aureus and Acinetobacter baumannii and also household bacteria like Escherichia coli genome-MDR-islands were sequenced confirming the calamity (see, fig. 3).

[pic 3]

That is not the end, porin membrane proteins were also mutated in such a way that antibiotics receptors were altered and no drug could enter into bacteria at low drug concentration giving MDR. Further, ribosomal ribonucleic acids (23S, 16S rRNAs) were gathered few mutations (usually very conserved) and many ribosomal proteins and drugs interactions did altered causing MDR. On one word, bacteria have achieved many shrouds against antibiotics and drug companies did not know where to start [8,9].

As for example, we discovered at least twenty types bacterial beta-lactamases (mdr genes) that were sequenced (10). Again in each type beta-lactamase gene, hundreds of mutations were discovered that sometime gave high drug resistance increasing drug MIC or totally resistant (4,10). GenBank analysis clearly showed that each conjugative plasmid in Pseudomonas aeruginosa, Klebsiella kneumoniae, Escherichia coli and Salmonella typhi had many mdr genes giving resistant to 5-10 antibiotics from different groups with different mode of ations (see, Table-1).

[pic 4]

Interestingly such plasmids carry mdr genes in one locus activated by transposon promoter-enhancers in most cases and Tra genes are located in cluster. It is very easy to isolate MDR bacteria in water by adding antibiotics in media at 50µg/ml. Then isolate plasmid DNA by alkaline lyses method and then do PCR reactions in presence of mdr gene specific primers and PCR product could be confirmed by di-deoxy DNA sequencing (11, 12).

.[pic 5]

Conclusion

Thus superbugs were highly contaminated in water resources of and rest of the world. G20 leaders at Berlin (May 2017) and now in Germany (July 2017) to formulate the action plan against MDR bacteria spread. WHO warned that if alternative to antibiotics would not discovered, very fatal human loss might be occurring in the future? Likely herbal antibiotics research has given priority in India as there is enough medicinal plants and spices available as described in Sanskrit books Charaka Samhita, Sasruta Samhita and Veda. New technologies like gene medicines (ribozymes, miRNA, antisencse RNA, and DNA nanotechnology) have been welcome to stop the horror of MDR bacterial pathogenesis.

Acknowledgement: I thank Dr J. B. Medda for financial support.

References

[1] Chakraborty AK (2016). Multi-drug resistant genes in bacteria and 21st Century problems associated with antibiotic therapy. Biotechnol. Ind J. 12(7):113.

[2] McArthur A. G., Waglechner N., Nizam F. et al.(2013). The Comprehensive Antibiotic Resistance Database. Antimicrob Agents Chemther., 57(7): 3348-3357.

[3] Drawz SM, Bonomo RA. (2010). Three decdes of beta-lactamase inhibitors. Clinical Microbiol. Review. 23:160-201.

[4] Xu, Z. Q., Flavin, M. T. and Flavin, J. (2014). Combating multi-drug resistant gram-negative bacterial infection. Exp. Opini. Investi. Drugs, 23: 163-182.

[5] Laxminarayana R (2014) Antibiotic effectiveness: Balancing conservation against innovation. Science. 345:1299-1301.

[6] Davis, J. and Davies, D. (2010). Origins and Evolution of Antibiotic Resistance. Microbiol. Mol. Biol. Revi. 74: 417-433.

[7] Okeke IN, Laxmaninarayan R, Bhutta ZA, Duse AG et al. (2005) Antimicrobial resistance in developing countries. Part 1: recent trends and current status. Lancet Infect Dis. 5:481-493.

[8] Chakraborty AK (2015) High mode contamination of multi-drug resistant bacteria in Kolkata: mechanism of gene activation and remedy by heterogenous phyto-antibiotics. Indian J. Biotechnol.14:149-159.

[9] Mckenna M (2013) The last resort: Health officials are watching in horror as bacteria become resistant to powerful carbapenem antibiotics-one of the last drug on the self. Nature 499: 394-396.

[10] Chakraborty AK (2016). Complexity, heterogeneity, 3-D structures and transcriptional activation of multi-drug resistant clinically relevant bacterial beta-lactamases. Trends Biotechnol-open access. 2: 1-001.

.

[11] Chakraborty AK. (2016). In silico analysis of hotspot mutations in the bacterial NDM-1 and KPC-1 carbapenemases that cause severe MDR phenotypes. Biochem. Biotechnol. Res. 4(1):17-26.

[12] Chakraborty AK (2017). Multi-Drug Resistant Bacteria from Kolkata Ganga River with Heterogeneous MDR Genes have four Hallmarks of Cancer cells but could be Controlled by Organic Phyto-extracts. Biochem. Biotechnol. Res. 5(1): 11-23.