Antimicrobial resistance is increasing, with a recent study by antibiotic research UK showing that resistance is already killing 700,000 people every year; a number which could rise to even 10 million by 2050 if the situation is not taken seriously. How is this happening?

Antibiotic resistance is the overarching process whereby bacteria become resistant to antibiotics (medication that would normally kill them). The issue can result in a number of antibiotics no longer being effective when taken by a patient to fight an infection. Due to this, many serious health issues can be triggered since your body will have to fight off the infection without the support of antibiotics, which results in a longer treatment period, potentially worse symptoms and side effects, and could even result in death if the body's immune system cannot fight off the infection sufficiently.

How does antibiotic resistance actually come about?

There are a number of different mechanisms by which bacteria can develop resistance to antibiotics. I shall outline three key examples in detail, and then provide some other methods which you can look into further if you are interested!

  1. Horizontal Gene Transfer (HGT): the sharing of genes between bacteria. There are three mechanisms of HGT: transformation, transduction and conjugation. Transformation occurs when bacteria take up DNA from its surrounding environment and integrate it into their overall genome. Transduction is a process whereby bacteriophage viruses inject viral DNA into bacteria. Finally, conjugation occurs when two bacterial cells engage in contact leading to the transmission of a plasmid (small circular loop of DNA) from one cell to the other through a cell membrane structure found in bacteria called the sex pili.
  2. Target Site Modification: when the target site of an antibiotic on the bacterium is modified. This is a very common mechanism that bacteria use to develop resistance to antibiotics. When bacteria copy their genome during replication, mistakes in the DNA sequence can occur. If any mutation(s) occur in a gene that encodes for a protein which is the target of an antibiotic, the antibiotic may no longer be able to bind to the target. Those with the mutation thus have a selective advantage, and reproduce, causing the mutation to spread further throughout the population as it grows.
  3. Efflux Pumps: obtaining additional efflux pumps as a result of the alteration of proteins that control the amount of efflux pumps produced, and hence chromosomal mutations can increase resistance. Efflux pumps pump a specific type of antibiotic outside of the bacterial cell, hence, lowering the intracellular antibiotic concentration. The overproduction of efflux pumps thus leads to an increased resistance to the drug targeted by the pumps.
  4. Intrinsic Resistance: where a bacterial species is naturally resistant to a certain antibiotic/family of antibiotics without the need for mutation or mutation of further genes - the 2 major mechanisms by which bacteria mediate intrinsic resistance are by differences in membrane permeability and access.
  5. Enzyme Inactivation
  6. Enzyme Modification: modify the target of the antibiotic or the antibiotic itself
  7. Replacement of the Target Site
  8. Overproduction of the Target
  9. Transposons: autonomous mobile genetic elements typically found integrated in the host chromosome; contain genes that enable them to integrate and excise from the chromosome
  10. Mixed Mechanisms

With the current situation revealing bacterial species that are resistant to all or almost all available antibiotics, the crisis is becoming more and more concerning. One key example of this are carbapenem-resistant enterobacteriaceae (CRE), which have become resistant to all/nearly all currently available antibiotics, including carbapenems. Carbapenems are a class of antibiotics typically reserved for final use/last resort, so when bacteria become resistant to these too, the situation's worrying nature deepens significantly.

Global Perspectives

A few key points to consider when evaluating the crisis relating to antimicrobial resistance:

  • We, as citizens of Earth, need to work together as a team to tackle this crisis - investing money into it and ensuring that every country, and person, has equal access to antibiotics where they are needed, but also to the medical expertise to inform whether or not antibiotics are actually required for a certain condition
  • Usage is a big issue - farmers are known to use a lot of antibiotics, but to what extent is unknown (they are used for prophylaxis, treatment, etc.). Recently, through the Ministry of Livestock, Agriculture and Fisheries (UK), the addition of antimicrobials to food for animal feeds has been almost entirely outlawed
  • More antimicrobial resistance occurs in cities compared with rural sites due to more readily available access to antimicrobials.
  • Buying antibiotics over the counter without prescription is illegal (UK) - laws are there against that are we are unable to effectively carry out mandates in order to enforce them. There is a lot of misuse and abuse of antibiotics in that context.
  • We do not always have enough data to convince policy makers regarding the big issue of antimicrobial resistance - for example in the UK, there is currently no national surveillance programme to collect data consistently.
  • Kenya's government adopted the National Action Plan that emanated from the Global Action Plan - if implemented fully, the five main objectives will ensure that we are able to start to tackle antimicrobial resistance there.
  • New technologies to perform surveillance faster and gather data much faster on usage in both humans and livestock must be developed. We also need the facilities to collect data on how many antibiotics are used in hospital, in the community, and more importantly for what purpose as well as how much is misused.

Some key take home messages from this relatively short article:

  • Ensure to finish your entire course of antibiotics if you are prescribed them, regardless of whether you feel better or not after say half of your course. Stopping the course part way through could lead to the bacteria being able to develop more resistance against that antibiotic.
  • Only take antibiotics when they are prescribed to you by a licensed medical professional and hence issued by a pharmacist. If you believe that you may not require the antibiotics, remember that it is always okay to ask questions. If you do truly need them, the medical staff will be able to explain why and put your mind at ease.
  • Keep spreading the message of how serious this issue is - hopefully with lots of media attention, the issue may be addressed more frequently around the globe in order to reduce the issue before we see the issue spiral completely out of control. Take part in WAAW (detailed below) at your school/university/work place! Find a link to the WAAW page in the references!

Remember! World Antimicrobial Awareness Week (WAAW) 2021: 18th November - 24th November

5 important goals of WAAW as outlined by the WHO:

  1. Raising awareness about antibiotics
  2. Increasing research and supervision
  3. Reducing infections
  4. Using antimicrobial medications the right way
  5. Committing to continual investment
“Antibiotic resistance occurs when bacteria change in response to the use of these medicines. Bacteria, not humans or animals, become antibiotic-resistant.” - WHO

I hope this article was useful and an interesting read - check back tomorrow for yet another instalment on biochemistree! Up next: "Are Viruses Alive?"

References

Antibiotic Research UK  About Antibiotic Resistance [online] Available At: https://www.antibioticresearch.org.uk/about-antibiotic-resistance/ Date Last Accessed: 05/12/2020
Lambert, P.A. (2005) Bacterial resistance to antibiotics: Modified target sites Advanced Drug Delivery Reviews doi:
10.1016/j.addr.2005.04.003
von Wintersdorff C.J.H., Penders J., van Niekerk, J.M., Mills, N.D., Majumder, S., van Alphen, L.B., Savelkoul, P.H.M. and Wolffs , P.F.G. (2016)
Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer Frontiers in Microbiology doi:
10.3389/fmicb.2016.00173
Webber, M.A. and Piddock, L.J.V. (2003)
The importance of efflux pumps in bacterial antibiotic resistance Journal of Antimicrobial
Chemotherapy doi: 10.1093/ jac /dkg050
Wellcome Genome Campus Advanced Courses and Scientific Conferences
Mechanisms of resistance Retrieved From FutureLearn:
https://www.futurelearn.com/courses/introduction-to-bacterial-genomics/6/steps/831670 Date Last Accessed: 05/12/2020
Wellcome Genome Campus Advanced Courses and Scientific Conferences
Resistance through chromosomal mutation Retrieved From FutureLearn: https://www.futurelearn.com/courses/introduction-to-bacterial-genomics/6/steps/831671 Date Last Accessed: 05/12/2020
Wellcome Genome Campus Advanced Courses and Scientific Conferences
Resistance through horizontal gene transfer Retrieved From FutureLearn: https://www.futurelearn.com/courses/introduction to-bacterial-genomics/6/steps/831672 Date Last Accessed: 05/12/2020

Who.int. 2021. World Antimicrobial Awareness Week. [online] Available at: https://www.who.int/campaigns/world-antimicrobial-awareness-week Date Last Accessed: 17/09/2021