Superbugs is we, the people. Well, the original

Superbugs IntroductionWe all are aware of the existence of microbes or microorganisms. They are present literally everywhere. From the deep-sea vents and volcanoes, to right inside me and you. They can survive and thrive anywhere!And now, the nemesis of bacteria, the antibiotics, are defeated.

Yes, the bacteria have evolved to flourish even in the presence of antibiotics. What is ‘super’ about Superbugs?Simply put, super bugs are basically bacteria which have developed antibiotic resistance. They can be resistant to one, or even multiple antibiotics and drugs.The problem which it creates is that if a superbug infects you, we cannot treat it as the bug is already resistant to the drugs which are available to us for treatment. You may die of overdosing on the drugs, but it won’t harm the bacteria and that is what the problem is, a lack of treatment. The source of powerYou may be wondering what is the source of this superpower. Well then, it is we, the people.Well, the original source will be mutation or acquiring the resistance from another microbe or gene pollution, nevertheless, their widespread proliferation is due to human actions.

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Whenever we have fever, cough, cold or any minor issue, we and our respected doctors jump straight into the antibiotic cabinet, even if the body’s immunity is more than capable to fight minor infections off in a couple of days. This abuse of antibiotics put selective pressure for the resistant strains to grow. And hence, rapid increase in the population of the drug resistant superbugs.In some cases, a superbug may develop resistance to even more drugs and antibiotics. The deadly powerLet’s talk about MRSA, Methicillin-resistant Staphylococcus aureus. It is a multi-drug resistant strain of a relatively common staph infection.

It starts as painful red bumps and turn in to deep abscesses which needs surgical draining. The bacteria can burrow deep into the body, causing potentially life-threatening infections in bones, joints, surgical wounds, the bloodstream, heart and lungs. It usually affects immunocompromised patients in hospitals and is very lethal. Worst of all, there is no cure for MRSA.Some other common superbugs are:o   Carbapenem-Resistant Enterobacteriaceae (CRE): Non-resistant strains are found in stomach, and resistant ones can enter in blood streams. They are resistant to all antibioticso   Multidrug-Resistant Acinetobacter baumannii: Found in soil, water and skin.

It develops a resistance to antibiotics more quickly than other bacteria and is most common in hospitalso   Neisseria gonorrhoeae: Resistant strain of gonorrhoeaeo   Clostridium difficile: Found in intestines. It can overgrow and cause severe diarrhoea. If untreated, it can be fatal. So much for antibiotic abuse, right? The Nemesis: AntibioticsHistorySir Alexander Fleming discovered the first antibiotic, Penicillin, which is derived from Penicillium notatum, which is an ascomycetes fungus, in 1928.

After mutation selection. Penicillium chrysogenum was developed with 100 times higher production of Penicillin.In 1942 Ernst Chain, Howard Florey and Edward Abraham purified the Penicillin, Penicillin G (Benzylpenicillin).And since then, BOOM! Since then, 270 new drugs were developed by 1970s and by 1990s, at least 18 major pharmaceutical companies were researching new antibiotics development. Classification of Antibiotics1) Penicillins: penicillin and amoxicillin2) Cephalosporins: cephalexin3) Macrolides: erythromycin, clarithromycin, and azithromycin4) Fluoroquinolones: ciprofolxacin, levofloxacin(Levaquin), and ofloxacin5) Sulfonamides: co-trimoxazole (Bactrim) and trimethoprim6) Tetracyclines: tetracycline and doxycycline7) Aminoglycosides: gentamicin (Garamycin) and tobramycin The problemA 2002 analysis published in Clinical Infectious Diseases found out that out of 506 drugs which were being developed, only five were antibiotics. Among those 89 drugs were FDA approved and released in the market, with neither of them being the antibiotic.According to a report by Pew Charitable Trusts, there hasn’t been a new class or type of antibiotic since 1984.

That is a gihugic problem as when a bacterial strain is resistance to an antibiotic, it extents to the whole class of the antibiotic. Any solution? There are three extremely promising strategies which scientists have come across on:  1) SNAPPsSNAPP stands for Structurally Nanoengineered Antimicrobial Peptide Polymers. They are peculiarly star-shaped proteins. As conducted in University of Melbourne, Australia and published in the journal, ‘Nature Microbiology’, they have been used to kill six different stains of drug resistant superbugs.

This approach is used to directly inflict damage on the bacteria, rather than in an indirect manner like antibiotics.The molecule has 16-32 arms which interacts with the cell wall of the bacteria. The molecule breaks the cell wall and disrupts it, leading to increased stress to the bacteria and hence death.Another advantage of this method is that the SNAPPs are about 10 nanometres in diameter and cannot enter the healthy cells, leaving them toxin or damage free.This technique was experimented on six different superbug strains of common and yielded brilliant results. This was taken forward to a model in mice too (using Acinetobacter baumannii). The best part is that even after several generations of growth, the microbes do not develop resistance to SNAPPs. A win-win situation here! 2) PPMONew Delhi Metallo-beta-lactamase (NDM-1) is an enzyme which plays a central role in spreading of antibiotic resistance in microbes.

Among all the available antibiotics, carbapenems are the ones for which least number of resistance strains exists.When NDM-1 is expressed, it goes and destroys the penicillins(including carbapenems) and hence rendering the bacteria resistance to these antibiotics.To tackle this problem, PPMO can be used. PPMO stands for Peptide-conjugated Phosphorodiamidate Morpholino Oligomer.The PPMO molecule inhibits the expression of NDM-1 gene and the lactamase isn’t produced. Since the enzyme is not produced, antibiotic resistance is nullified.

The researchers firstly used naturally occurring PPMOs, but the backdrop was that each PPMO molecule was specific to one genera at maximum. To overcome this, they synthesized an artificial PPMO which works perfectly with at least three genera which have developed resistance to carbapenems.They also tried this on mice. They infected the mice with meropenem(a type of carbapenem) resistant Escherichia coli.

Then they injected them PPMO and doses of meropenem. They observed that the bacteria lost it capacity to produce NDM-1 lactamase and were killed by meropenem.The human trials haven’t started yet, but the method is expected to be approved within three years.The study was conducted in Oregon State University and published in the Journal of Antimicrobial Chemotherapy.

 3) DNA Reprogramming Another novel approach take up by scientists is to edit the resistance providing genes in a way that it renders the gene silent. This is done using CRISPR/Cas systems to selectively cleave the antibiotic resistance gene disenabled. Since the enzyme linked to antibiotic resistant is now not being produced, the bacteria now is susceptible to the antibiotics it was resistant against.The research is led by Professor Udi Qimron of the Department of Clinical Microbiology and Immunology at TAU’s Sackler Faculty of Medicine. ConclusionSuperbugs are indeed very dangerous and are merciless killers. In this battle we are the underdogs. If we are to overpower them, more detailed, refined and conclusive research is to be done in treating them. Also doctors and people need to learn that abusing antibiotics for each and everything is the worst idea for the mankind and must be avoided at all costs.

After all, “prevention is better than the cure”! 


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