How a garden gate could help your post takeaway food poisoning

The YddA transporter found in Escherichia coli (E. coli) may have a direct involvement in the export of antibiotics or virulence factors back out of the E. coli cell once they have penetrated- this would cause antibiotic resistance in the bacteria and allow it to cause more issues when infecting a human host.

Ever wake up the morning after a delicious Chinese and suddenly you can feel your intestines not agreeing with you? This is a well-known side effect of fast food consumption and is commonly caused by a type of bacteria called (E. coli). This pesky type of bacteria is abundant and has evolved multiple ways to cause medical issues in human and animal bodies alike.

My MSci dissertation project is focused on studying this specific channel found within its membrane walls. This channel lets in or lets out chemicals within the cell and acts just like a garden gate. The name of this gate is YddA (not the catchiest name I know) and by studying this gate, we may be able to design drugs that weaken or deactivate the bacteria.

Figure 1. A schematic representation of the hypothesis for my research project
In a simplified representation, the YddA channel is a transporter at the E. coli cell membrane which is able to export antibiotics from the cell. This leads to the antibiotics not working against the cells and the infection continues to worsen. If a drug could block YddA, this could lead to the antibiotics being stuck inside the cell and having harmful effects- slowly weakening the cell and leading to cell death, and eventually infection resolution.
Image created by the author at https://biorender.com/

So far, very little is known about this gate, and what it exports remains a mystery. My research will aim to discover is whether or not it exports antibiotics or toxic substances that have made their way into E. coli. If the channel does export antibiotics back out of the cell, this would benefit E. coli by reducing the intracellular concentration of that antibiotic and alleviates the effects of it- allowing it to resist that course of penicillin antibiotics your doctor gave you. This would be a significant factor to the widespread medical concern about antibiotic resistance.

Different antibiotics will be tested against samples of this bacteria- with the YddA channel present in the genome. If the organisms are resistant to any of them, then they show antibiotic resistance. The gene that writes the code for this specific channel will be essentially ‘deleted’ and the newly grown, non-YddA containing, bacteria will once again be combined with the antibiotic(s) they were previously resistant to. If they are then killed by the antibiotic(s), i.e. not showing resistance to it anymore, this will be tangible evidence that YddA exports the harmful antibiotic out of the organism after it has penetrated through its membranes.

Figure 2. A schematic representation of my main experiment
In a simplified representation, 11 different antibiotics that have not been tested against YddA previously by other scientists will be added to E. coli containing the ydda gene. It is expected that at least 1 of these will be resisted by the bacteria and so this antibiotic(s) will then be tested against E. coli not containing the ydda gene. If the resistance that was observed in the first part of the experiment is now not present, it can be reasonably suggested that YddA is the mediator of resistance to this antibiotic.
Image created by author at https://biorender.com/

After this research has been completed, it should be clear what function this tiny little gate has in E. coli, and this will lead to future medical advancements that may reduce the effects this bacteria has in the general population. Saving you those hours spent regretting your Friday night Chinese.

Bibliography for further reading:

  • “Escherichia coli Sequence Type ST131 as the Major Cause of Serious Multidrug-Resistant E. coli Infections in the United States”, Johnson, J.R., Johnston, B., Clabots, C., Kuskowski, M.A. & Castanheira, M. 2010, Clinical Infectious Diseases, vol. 51, no. 3, pp. 286-294 https://pubmed.ncbi.nlm.nih.gov/20572763/
  • “Novel Macrolide-Specific ABC-Type Efflux Transporter in Escherichia coli”, Kobayashi, N., Nishino, K. & Yamaguchi, A. 2001, Journal of Bacteriology, vol. 183, no. 19, pp. 5639-5644 https://pubmed.ncbi.nlm.nih.gov/11544226/
  • “Scanning the Escherichia coli chromosome by random transposon mutagenesis and multiple phenotypic screening”, Serina, S., Nozza, F., Nicastro, G., Faggioni, F., Mottl, H., Dehò, G. & Polissi, A. 2004, Research in Microbiology, vol. 155, no. 8, pp. 692-701 https://pubmed.ncbi.nlm.nih.gov/15380559/
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October 29, 2020
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