Antibiotic resistance is (not) futile

The evolutionary race between humans and bacteria has been raging on for millions of years but what happens when you inadvertently give the enemy a helping hand…. 

Author: Victoria Afrah Danquah
Editor: Diana Coroi
Artist: Amy Zhang


Anyone familiar with the popular, disturbingly accurate pandemic simulation game, Plague Inc., will know that acquiring antibiotic resistance is one of the most powerful tools you can use to strengthen your pathogen and decimate the human population. But how dangerous is it in real life?

Long story short, very. The World Health Organisation has declared antibiotic resistance as one of the top three most important health threats of the 21st century. Furthermore, the UK government has predicted that, by 2050, antibiotic resistant infections will be responsible for 10 million deaths per year, more than all cancer deaths combined.

Antibiotic resistance is the mechanism pathogens use to become resistant to many drugs normally used to treat common infections, rendering them without an effective treatment. This means that minor health nuisances such as bronchitis and ear and skin infections have the potential to develop into deadly diseases such as toxic shock syndrome, sepsis and pneumonia.

One of the most infamous antibiotic resistant bacteria, Methicillin Resistant Staphylococcus Aureus, also known as MRSA, peaked at 1,652 deaths in England and Wales in 2006, but has since been on a decreasing trend, thanks to changes in clinical practice.

There are two main methods that bacteria use to gain antibiotic resistance: Mutational resistance and Horizontal Gene Transfer (HGF).

Mutational resistance: a small population of bacteria can develop a random genetic mutation that can inhibit or evade the action of a drug. For example, in the presence of β-Lactam antibiotics such as penicillin, MRSA develops changes to the structure of its cell wall so that penicillin can no longer target it. This new drug–resistant mutation allows the bacteria to survive and multiply in the presence of antibiotics, eventually colonising the non-resistant population. The new mutation often makes the first and second lines of infection treatment ineffective.

Horizontal Gene Transfer: when foreign DNA is transferred from one pathogen to another. This can be seen as sexual reproduction for bacteria. While antibiotic resistance is a natural process, human activity has greatly exacerbated the issue.

One possible factor is the excessive use of antibiotics in farm animals. An independent report by economist Jim O’ Neill, commissioned by the UK government in 2015, found the following risks:

  • In the US, more than 70% of all medically important antibiotics are used on farm animals
  • Drug resistant strains can be passed onto humans via animal contact
  • Drug resistant strains can be passed onto humans by eating the meat of antibiotic resistant animals
  • Drug resistant strains can be spread into the environment through exposure to excrement. This poses the greater risk of spreading community-based infections, since water from irrigation can cause excrement to infect rivers and drinkable water supplies.

These concerns have already begun to take shape. In 2006, the cause of a spinach E. coli outbreak in the US was traced back to crop water irrigation, believed to have been contaminated by pig and cow manure. This outbreak resulted in three deaths.

Using antibiotics allows animals to grow fatter without increasing their food supply, so it is a very cost-effective practice in the farming industry. Farmers in developing countries may be more reliant on these methods, as a constant supply of quality animal feed is not always available. 

There are currently clinical trials taking place to test novel treatments for antibiotic-resistant infections, such as antimicrobial peptides. Their mechanisms for destroying bacteria include inhibiting protein synthesis via DNA and RNA inhibition and disrupting the bacterial cell membrane by forming pores in the membrane. By selecting amino acids with certain properties, these peptides can have a higher affinity for bacterial cells than human cells, thus resulting in low toxicity in humans This will help the positively charged antimicrobial peptides to tell the difference between the bacterial and human cells.

While there is a demand for new antibiotics, developments of such treatments are putting a huge strain on pharmaceutical companies, with development costs reaching over $1 billion and a failure rate of 95% for most potential antibiotics. One solution to filling this funding gap is the introduction of insurance premiums with fixed annual payments that will go towards helping new antibiotics become available on national health systems such as the NHS. Other ideas include a funding program that will help make new antibiotics available while helping pharmaceutical companies recoup any financial losses. Most governments have been reluctant to implement these plans in recent years due to the significant costs of such measures.

Antibiotic resistance is a complex matter both biologically and economically, which makes for a fun addition to a thrilling and nihilistic game about human extinction, but also a disaster that can be just a few genetic mutations away. Some food for thought next time you play a round of Plague Inc.  

References

Burmeister, A. R. (2015) ‘Horizontal Gene Transfer’, Evolution, medicine, and public health. Oxford University Press, 2015(1), pp. 193–194. doi: 10.1093/emph/eov018.

Malmsten, M. (2014) ‘Antimicrobial peptides’, Upsala journal of medical sciences. 2014/04/23. Informa Healthcare, 119(2), pp. 199–204. doi: 10.3109/03009734.2014.899278.

Moyer, M. W. (2016) How Drug-Resistant Bacteria Travel from the Farm to Your Table, Scientific America. Available at: https://www.scientificamerican.com/article/how-drug-resistant-bacteria-travel-from-the-farm-to-your-table/ (Accessed: 1 December 2016).

Munita, J. M. and Arias, C. A. (2016) ‘Mechanisms of Antibiotic Resistance.’, Microbiology spectrum. United States, 4(2). doi: 10.1128/microbiolspec.VMBF-0016-2015.

NHS (2015) Antibiotic use in farm animals ‘threatens human health’, NHS. Available at: https://www.nhs.uk/news/medication/antibiotic-use-in-farm-animals-threatens-human-health/ (Accessed: 9 December 2015).

Olatunde, O. (2013) Deaths involving MRSA: 2008 to 2012, Office of National Statistics.

Peacock, S. J. and Paterson, G. K. (2015) ‘Mechanisms of Methicillin Resistance in Staphylococcus aureus’, Annual Review of Biochemistry. Annual Reviews, 84(1), pp. 577–601. doi: 10.1146/annurev-biochem-060614-034516.Trust, W. (no date) Drug resistant infections: the science is on track, but the economics needs fixing, Wellcome Trust. Available at: https://wellcome.ac.uk/what-we-do/our-work/drug-resistant-infections/drug-resistant-infections-science-economics.

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