A Game of Antibiotics and Superbugs

Image Credit: Unsplash: CDC

Tatyana Sinaisky discusses how antibiotics were first discovered and how our dependence and over-use of them ultimately led to the evolution of highly drug-resistant bacteria called ‘Superbugs’.

When on the subject of antibiotics, most are aware of Sir Alexander Fleming, a Scottish physician who first discovered penicillin. In 1928, before setting off on a family holiday, Fleming left an uncovered Petri dish housing a colony of the common staphylococcal bacteria sitting by an open window. Upon his return, Fleming remarked that his Petri dish had become contaminated with mould spores. The peculiar part? The bacteria in close proximity to the mould spores were dying. Curious, he isolated the mould and noted its effectiveness against all gram-positive pathogens, known today for illnesses such as pneumonia and gonorrhoea. Penicillin was discovered and the treatment of infectious diseases was about to be forever altered.

Antibiotics seemed to be winning the battle against pathogenic bacteria, unaware that the superbugs were preparing for a major retaliation.

A History: 

If we take a deeper look at the discovery of antibiotics, however, Sir Fleming was not the first to come across these antimicrobial substances. The term “antibiosis” was first coined by the French mycologist Jean Paul Vuillemin, meaning “against life”. He described this proposed mechanism as “one creature destroying the life of another to sustain its own.” Ironic, yet logical.

Arsphenamine, an arsenic derivative, more widely known as Salvarsan, was discovered in 1910 by German scientist Paul Ehrlich and used as an antibiotic to treat the STI (Sexually Transmitted Infection) syphilis. Although its discovery and public deployment preceded that of penicillin, it is often neglected in this tale. This antibiotic enjoyed commercial success for only a brief period of time as potentially fatal side effects came to light such as the development of concurrent illnesses, namely chest infections and genital herpes, and showed marked toxic effects in patients with conditions such as meningitis. Only a few decades following the discovery of Salvarsan was it replaced with the “safer” antibiotic, penicillin, in the treatment of syphilis. Nonetheless, Ehrlich’s discovery of Salvarsan paved the way for the discovery of several other antibiotics. 

Following Sir Fleming’s ground-breaking discovery of penicillin, scientists Ernst Chain and Howard Florey went on to purify the first penicillin, penicillin G in 1942, enabling the antibiotic to become widely produced to treat an array of bacterial illnesses. The three men shared a Nobel Prize in 1945 for their contribution to medicine. 

The 1950s to 1970s was the golden age of novel antibiotic discovery, from vancomycin to carbapenems, this era revolutionised the treatment of infectious diseases worldwide. The leading cause of death in Ireland changed from communicable diseases, such as tuberculosis and pneumonia to non-communicable diseases, most notably cancer and cardiovascular diseases. 

The discovery of antibiotics, coupled with the introduction of vaccines, increased sanitation and education have all contributed to the increased life expectancy of humans, especially in developed countries. However, developing countries are also seeing a gradual improvement. Nature though has a habit of throwing an obstacle in the course of evolution when we least expect it, to ensure a strict balance in the world. Antibiotics seemed to be winning the battle against pathogenic bacteria, unaware that the superbugs were preparing for a major retaliation. 

As we mutate, so will the bacteria, but it is unlikely that we will mutate into something completely different, thus keeping the bacteria in check for now

An Evolving War: 

Bacteria are the miniscule masters of survival. In the little time since the discovery and usage of antibiotics, they have evolved to protect themselves. 

In the late 1940s Mary Barber, a professor of clinical bacteriology, found that Staphylococcus aureus, which can cause skin and soft tissue infections started to show resistance to Celbenin, an antibiotic derivative of penicillin previously used in severe staphylococcal infections. Blind optimism during this era regarding the pharmaceutical industry’s ability to keep up in this microbial arms race fed our complacency, overriding any drive to combat this “resistance”.

Through a collection of observations in Japan in the 1960s, notably those of Dr Tsutomu Watanabe who remarked on the evolution of antibiotic resistance in fish stock, scientists began to collectively agree that resistance was becoming a cause for concern and that something would have to be done fast if we did not wish to succumb to antibiotic resistance. 

So, what is antibiotic resistance? Darwin’s Theory of Natural Selection suggests that organisms can undergo random mutations, many insignificant. Every so often though, a mutation gives an organism an edge to survival and as time goes on, these better-adapted organisms are produced to fill in the shoes of their previous ancestors. Bacteria have developed several ways to resist antibiotics. Some exchange plasmids, a type of bacterial DNA, to share useful abilities which aid survival while others use a process called “transformation”, allowing bacteria to collect genetic material from their environment, such as that from other dead bacteria. The unnerving part about the latter process is that it even works between different species of bacteria, giving rise to ‘superbugs’ as well as bacterial immunity against multiple antibiotics. 

As the non-resistant bacteria are killed off by antibiotics, resistant bacteria are given room to thrive. Hospitals are breeding grounds for superbugs with their intensive use and over-prescription of antibiotics in many patients. Incorrect usage and poor disposal of antibiotics also contributed to the rise in superbugs. Finally, antibiotic use in meat production is another contributor to this problem as livestock held in overcrowded and unhygienic conditions, creating a cosy lodgement for bacteria, are given antibiotics to prevent them from getting sick. These conditions also ensure that the price of meat remains affordable.

A Sign of Hope: 

In an interview with the University Observer, Assistant Professor Jennifer Mitchell from the School of Biomolecular and Biomedical Sciences in UCD discussed how superbugs evolved and what potential treatments we can use to combat them.

Dr Mitchell explained that humans are in fact not fully to blame for the development of superbugs. Danish scientist Jesper Larsen and colleagues have tracked the evolution of one type of Methicillin-Resistant Staphylococcus Aureus (MRSA) to hedgehogs hundreds of years ago through natural selection, long before the era of antibiotic use. It is clear that the use of antibiotics accelerates resistance, but Dr Mitchell explained that these spiny mammals may give us a new vantage point to study antibiotic resistance and the potential for new beneficial discoveries.

When asked about the use of bacteriophages as an alternative treatment option, Dr Mitchell explained that although it has been shown to work “fantastically well” for some people, such as in that of Thomas Patterson in UC San Diego, this is still highly experimental and the ultimate form of personalised medicine. Bacteriophages are a type of virus that kill bacteria by invasion and rapid reproduction. Due to the specificity of this treatment, it is not a guaranteed victory in our battle against antibiotic resistance. More research is needed, but this is already proving to be a challenge as pharmaceutical companies remain reluctant to invest in such experimental treatment. Nonetheless, the attention that bacteriophages are receiving is something that we may be able to take as a sign of hope in this battle against superbugs.

Mother Nature holds the upper hand as humans and bacteria continue to play a relentless and savage game which is still in its early days.

As NASA prepares to send humans to Mars, potentially for continuous habitation, the question as to whether bacteria will dramatically mutate outside of Earth is raised. Dr Mitchell explained that bacteria require our metabolism to work effectively. As we mutate, so will the bacteria, but it is unlikely that we will mutate into something completely different, thus keeping the bacteria in check for now. She also discussed how some bacteria have theoretically survived space travel, but show no dominance just yet. The reason being, once again with reference to Darwin, is due to competition in nature.

In just over 100 years, the treatment of infectious diseases has been revolutionised thanks to huge advancements in modern science. Scientists continue to work persistently to ensure that we remain one step ahead, whether it is through antimicrobial therapy, vaccines or something completely different that is just on the cusp of discovery. Nevertheless, Mother Nature holds the upper hand as humans and bacteria continue to play a relentless and savage game that is still in its early days.