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Proposal Requirement 4 Example: Combating Antibiotic Resistance

Writer: Jana Chan

Instagram: @janabanana_chan

Email: jana.chan28@gmail.com


Current Solutions and Their Insufficiencies

With antibiotic resistance growing in an increasing number of bacteria, there are currently four main solutions being investigated to fight it (Allen, 2017; Ghosh, Sarkar, Issa, & Haldar, 2019). The first, and what is currently most heavily researched, is bacteriophage therapy. In this method, bacterial viruses, called phages or bacteriophages, bind themselves to the enemy bacteria and kill it by causing the bacteria to burst through the lytic or lysogenic cycle. The phages infect the bacteria by injecting its genes so it can reproduce inside the bacteria. About 1000 new phages are produced, and when it breaks the bacteria open, these new phages are released. Phage therapy has been around for a century, starting when Felix d'Herelle coined the term bacteriophage in 1915, but even then, not enough is known (D. Lin, Koskella, & H. Lin, 2017). However, some basic advantages and disadvantages can be seen from a 2011 study (Loc-Carillo & Abedon, 2011). Most importantly, phages can work against both treatable and antibiotic-resistant bacteria. Moreover, phages can grow their population easily, so only one dose may be needed, thus lowering misuse. This method will also harm the beneficial bacteria already in the body only marginally, whereas antibiotics often come with negative side effects. Finally, phages are easy to find and are typically seen in sewage or places with high bacterial concentration. The biggest disadvantage is simply that more research needs to be done on how it will react in humans and animals. Bacteriophage therapy has not been approved in the United States or Europe, and only a small number of experimental trials have been done, as antibiotics have become so prevalent. It is still unclear whether bacteria can become phage resistant, if phages can be used against all types of bacteria, the dosage that should be used, how long phage therapy needs to work, and if the immune system will react negatively. Furthermore, phages can only multiply inside bacteria, so they are dependent on a bacterial host (Lin et al., 2017).

Discovered by André Gratia in 1925, the second solution available are bacteriocins, which are peptides that can be produced by both gram-positive and gram-negative bacteria. Not only are they highly potent and contain low toxicity, but bacteriocins are also heat-stable and can be bioengineered. The genes of bacteriocins are encoded on a plasmid and can enter other bacteria through conjunction, allowing for the spread of bacteriocins within a bacterial population. With the ability to target the cell membrane and other cell functions, such as bacterial DNA, RNA, and protein metabolism, with impressive specificity, bacteriocins seem to be a viable alternative to antibiotics (Cotter, Ross, & Hill, 2013). They have already proved to be an extremely effective “anti-cancer” drug in fighting tumor cells, and if further research is done, could replace antibiotics (Yang, Lin, Sung, & Fang, 2014). However, there is a possibility that bacteria could be resistant to bacteriocins. Several papers have proposed mixing different bacteriocins or even creating bacteriocin and antibiotic combinations to create a “cocktail” of drugs, but there is such a vast array of pathogens and multi-drug resistant bacteria that it will take a significant amount of time to find the safest and most effective combination. (Yang et al., 2014).

Antimicrobial peptides (AMPs), also referred to as host defense peptides (HDPs), are short, typically positively-charged peptides (short chains of amino acids) that can be found in a variety of living beings from microorganisms to humans. An advantage to AMPs is their abundance, with more than 880 different species of AMPs already discovered or predicted based on their nucleic acid sequences so far. As a part of the natural immune response found in most life forms, these AMPs can directly and rapidly kill bacteria. (Brogden, 2005). To do this, the peptides will interact with the bacterial membrane to disrupt the physical integrity of this membrane and ultimately translocate across it. It will then be able to enter the cytoplasm of the bacteria and alter the bacteria’s intracellular organelles (Mahlapuu, Håkansson, Ringstad, & Björn, 2016). This solution has long been considered to be a viable alternative to antibiotics but has had a low success rate in clinical trials (Ghosh et al., 2019). While there have certainly been many scientific journals proposing AMP strains as potential drug candidates, there continues to be a large disparity between these proposals and the actual outcomes of clinical trials (Mahlapuu et al., 2016). Additionally, it is important to understand that this may only be a temporary solution, as there is a possibility that bacteria could also build resistance strategies against AMPs—similar to how bacteria have formed a resistance against antibiotics. By targeting the mechanisms that AMPs use to kill its prey, such as through countering antimicrobial peptide attachment, AMP insertion, and membrane permeability, bacteria might be able to build another defense that could undermine this solution (Brogden, 2005).

Finally, scientists are also considering the use of predatory bacteria, where bacteria fight bacteria. Many papers have already dubbed this a new “living” antibiotic, and much research has already been done in this area (Ulsan National Institute of Science and Technology [UNIST], 2017). This method utilizes the already existing traits of certain bacteria and the natural competition between bacteria populations. Above all, since the bacteria itself is such a significant portion of this method and because there are already trillions of bacteria in the human body, it would be easier and more convenient to find and test potential candidates. The way each bacteria kills its prey will vary, so studying each bacteria closely will be essential. Additionally, predatory bacteria will need to be able to protect itself from other bacteria, thus a defense system must either already exist in that bacteria or be created. It is also pertinent that predatory bacteria can differentiate between helpful and harmful bacteria, as killing beneficial organisms will be counterproductive. All of these constraints will need to be considered when this method is explored (UNIST, 2017).


Analysis

This example transitions nicely from the previous section by utilizing transition words such as first, finally, most importantly, and additionally. It thoroughly describes how each solution works, the constraints, and the advantages that come with each solution so that these factors can be analyzed in part 5 of the proposal. In terms of style and grammar, it is written clearly and concisely, making it easy to follow. Throughout the example, citations follow APA format and there is no usage of the first or second person (as this part discusses previous knowledge already explored by other scientists, not the process or results of the author). Moreover, by providing very brief histories of almost all the methods, the example gives the reader a reference point to understand that method’s evolution.

Figures and/or diagrams could have been used to enhance this example, as it would elaborate and provide details on certain aspects that may not be as effectively expressed through writing. For example, diagrams might be beneficial to illustrate the actual processes of each method and how it kills its bacterial prey.



References

  1. Allen, H. K. (2017). Alternatives to antibiotics: Why and how. NAM Perspectives. Discussion Paper, National Academy of Medicine, Washington, DC. DOI: 10.31478/201707g

  2. Brogden, K. (2005). Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nature Reviews Microbiology, 3, 238–250. https://doi.org/10.1038/nrmicro1098

  3. Cotter, P., Ross, R. & Hill, C. Bacteriocins — a viable alternative to antibiotics?. Nat Rev Microbiol 11, 95–105 (2013). https://doi.org/10.1038/nrmicro2937

  4. Ghosh, C., Sarkar, P., Issa, R., & Haldar, J. (2019). Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance. Trends in Microbiology, 4, 323-328. https://doi.org/10.1016/j.tim.2018.12.010

  5. Lin, D. M., Koskella, B., & Lin, H. C. (2017). Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World journal of gastrointestinal pharmacology and therapeutics, 8(3), 162–173. https://doi.org/10.4292/wjgpt.v8.i3.162

  6. Loc-Carrillo, C., & Abedon, S. T. (2011). Pros and cons of phage therapy. Bacteriophage, 1(2), 111–114. https://doi.org/10.4161/bact.1.2.14590

  7. Lopetuso, L. R., Giorgio, M. E., Saviano, A., Scaldaferri, F., Gasbarrini, A., & Cammarota, G. (2019). Bacteriocins and Bacteriophages: Therapeutic Weapons for Gastrointestinal Diseases?. International journal of molecular sciences, 20(1), 183. https://doi.org/10.3390/ijms20010183

  8. Mahlapuu, M., Håkansson, J., Ringstad, L., & Björn, C. (2016). Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2016.00194

  9. [Cover image: Predatory bacteria Bdellovibiro bacterivorous attacking its prey]. NPR. https://www.npr.org/sections/health-shots/2018/09/06/643661823/predatory-bacteria-might-be-enlisted-in-defense-against-antibiotic-resistance

  10. Ulsan National Institute of Science and Technology. (2017, March 21). Predatory bacteria as a new “living” antibiotic. Phys.org. https://phys.org/news/2017-03-predatory-bacteria-antibiotic.html

  11. Yang, S. C., Lin, C. H., Sung, C. T., & Fang, J. Y. (2014). Antibacterial activities of bacteriocins: application in foods and pharmaceuticals. Frontiers in microbiology, 5, 241. https://doi.org/10.3389/fmicb.2014.00241