THE GROWING THREAT OF ANTIBIOTIC RESISTANCE

By Shivas Patel

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Almost a century ago, a Scottish researcher by the name of Alexander Fleming returned from a holiday to an unpleasant sight – a blob of mould growing on one of his Petri dishes. Fleming almost discarded the dish, but upon closer inspection he noticed a clear ring around the mould where the usual array of bacterial colonies appeared to be absent. Immediately captivated by this ‘mould juice’, Fleming got to work experimenting on dozens of different types of harmful bacteria, recording his observations in the British Journal of Experimental Pathology over the next year. Although the implications of this accidental discovery excited Fleming, the researcher had little idea that his newfound drug penicillin would become the most widely used antibiotic in the world - instrumental in the treatment of countless bacterial diseases, including pneumonia, gonorrhoea and syphilis.

92 years later, it is impossible to imagine the world without penicillin. Its initial use during the Second World War enabled the almost instant treatment of previously fatal infections, like meningitis, preventing huge fatalities. Diseases that took years to recover from could now be forgotten in days. By the late 1940s, doctors were convinced that the cure to all bacterial diseases was on the horizon.

The bacterium Staphylococcus aureus was commonly treated using the ‘wonder-drug’ penicillin. But as the number of prescriptions increased, doctors began to notice huge increases in recovery times, as well as numerous patients who didn’t recover at all. It was quickly realised that a certain strain of the bacteria had mutated to become resistant to the antibiotic and that the rapid rate of the bacteria’s reproduction had led to overwhelming numbers of incurable cases. However, doctors were far from panicked, and simply opted to switch from penicillin to methicillin, another common antibiotic. This became the go-to treatment for S. aureus by the 1950s.

In 1961, British scientists revealed that they had discovered a strain of bacteria which was resistant to methicillin, which would in time become resistant to a variety of other related penicillin-related antibiotics as well, including beta-lactams. The alarming new ‘superbug’ was called Methicillin-Resistant Staphylococcus Aureus, or MRSA. This strain of bacteria was able to subdue and resist antibiotics which targeted peptidoglycans (components of the bacterium’s cell wall).

Amid fears that our ability to treat bacterial disease would go back to square one, the turn of the century saw an explosion of new research into the field of antibiotic resistance. New medical practices became commonplace across the world. Doctors were urged not to over-prescribe antibiotics, which fuelled the problem. Patients were told to finish the entire course of their antibiotic treatments, in order to completely eradicate the bacteria present.

Yet, to this day, the problem remains as formidable as ever – MRSA is the second-largest cause of death by drug-resistant bacteria in the United States. Pharmaceutical companies are abandoning research on antibiotics to favour newer and more ‘innovative’ drugs. With the emergence of COVID-19, antibiotic research at major institutions has more or less been deserted to allow for research into developing treatments to aid the current crisis.

In spite of this, scientists have not given up on antibiotics completely, and a range of new methods are being trialled. Researchers at Merck Research Laboratories in New Jersey were able to isolate two compounds called Tarocin A and Tarocin B, both of which target the teichoic acid portion of the bacterial cell wall. When combined with antibiotics and tested on mice, they were found to be kill MRSA bacteria. This method of treatment has been dubbed a ‘two-prong attack’ – where antibiotics are combined with other compounds to create a more potent treatment. Even so, the project’s head researcher Christopher Tan has expressed his concerns that MRSA could simply mutate again to become resistant to the double treatment, and hence research into a third drug, which would target another part of teichoic acid production, could be added to the mix. Similar approaches have been undertaken in experiments involving E. coli and various other bacteria, which have become resistant to the antibiotic beta-lactamase. E. coli possesses an enzyme which is able to break down the antibiotic, but certain compounds which inhibit said enzyme can be used to increase the effectiveness of beta-lactamase. Alternative methods of overcoming the threat of antibiotic resistance are also being explored, including the development of new antibiotics found in soil in California, the use of ‘good’ gut bacteria to outcompete the bacterium C. difficile in Massachusetts, and the development of synthetic antibodies used to target bacteria in place of antibiotics.

Despite the immense scientific concern surrounding the now imminent threat of antibiotic resistance, the process of researching new treatments and developing new drugs is an long and expensive one. It is apparent that this field will be forced to expand if we are to overcome the dangers of superbugs like MRSA, which could lead to even the most common treatments becoming ineffective in the near future, unless immediate action is taken.

Sources:

https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance

https://www.medicalnewstoday.com/articles/10634

https://www.healio.com/endocrinology/news/print/endocrine-today/%7B15afd2a1-2084-4ca6-a4e6-7185f5c4cfb0%7D/penicillin-an-accidental-discovery-changed-the-course-of-medicine

https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html#alexander-fleming-penicillin

https://www.newscientist.com/term/antibiotic-resistance/

https://www.newscientist.com/article/2080180-mrsa-superbugs-resistance-to-antibiotics-is-broken/

https://www.newscientist.com/article/2190957-the-war-against-antibiotic-resistance-is-finally-turning-in-our-favour/

https://www.livescience.com/40412-what-is-mrsa.html