The antibiotic resistance gene can “develop the ability to survive exposure to antibiotics designed to kill them” (yourgenome). The antibiotic resistance gene contains various mechanisms to block the acceptance of the effects of antibiotics and provides many usages in multiple fields.
Gene cloning is a great example that uses antibiotic resistance. Gene cloning is often explained as identical copies of pieces of DNA. Standard gene cloning performed with a copy of DNA strain and a plasmid and injected the performed plasmid into a bacteria. From the DNA strain, the chosen gene to clone will be cut by the restriction enzymes, and the gene to clone will be pasted in the plasmid by the DNA ligase. Finally, the modified plasmid will be placed in the bacteria as a small DNA container and undergo the cell culture process.
When scientists observe the numerous bacteria colonies, they confront the ultimate question: How can bacteria colonies be distinguished as bacteria that “perfectly contains the cloned gene” because some territories will take the characteristics. However, some colonies will not successfully possess the cloned gene.
Therefore, on the culture medium (the plate to grow the bacteria), the scientists put the nutrients to stimulate the growth and the antibiotic. Also, they insert the antibiotic-resistance gene into the plasmid, which will be placed in the bacteria. Only a colony of bacteria that has successfully possessed the plasmid with the cloned gene and the antibiotic resistance gene can survive the antibiotic on the culture medium.
How can the antibiotic resistance gene circumvent the antibiotic and survive? Furthermore, how can the antibiotic resistance gene be transmitted to other bacteria?
Defense Strategies of Bacteria (Germ)
Germs’ antibiotic resistance genes representatively use four different strategies to prevent the antibiotic substances.
Restricted access of the antibiotic
Pumping out the antibiotic
Change of the targets for the antibiotic.
Destroyal the antibiotic
Restricted access of the antibiotic
Bacterias use their membrane to minimize the number of entrances and modify the entries to restrict access to the antibiotic.
For example, in polymyxin antibiotics, when the charge difference is more significant than the repulsive forces, the polymyxin antibiotics will eventually be able to penetrate and create membrane (composed of lipid) damage" (Khondker, Rheinstädter). However, the two most important factors determining whether polymyxins can successfully insert into membranes are the electrostatic attraction and the "elastic: resistance of the membrane. Liu and colleagues researched that (-) charge PO4 -3 touching each lipid A converts to a neutral ethanolamine moiety in pathogens. As the negatively charged compound changes to the neutral compound, the charge will be reduced and block the antibiotic's attraction towards cation. Moreover, the increasing amount of the ethanolamine in the lipid strengthens the intermolecular force of the covalent bond in lipid-protein, causing hardship for antibiotics to enter the membrane.
Pumping out the antibiotic
Bacterias use an efflux pump in the cell membrane to get rid of the antibiotic which aims to enter the cell. When an antibiotic like tetracycline enters the membrane, which generally interferes with bacterial protein synthesis, the efflux pump pumps out the antibiotic, making the effect unworkable. Pseudomonas aeruginosa is a bacteria that uses a mechanism of tripartite RND-MFP-OMF efflux pumps, a kind of the multidrug efflux system. The MES, located in bacterial genomes to cure the infection. However, the role of MES is broad. MES "exports organic solvent, detergents, fatty acids, toxic lipids, and quorum sensing molecules" (Issa). The role of the efflux system in Pseudomonas aeruginosa related to the resistance gene also "gets rid of several different important antibiotic drugs, including fluoroquinolones, beta-lactams, chloramphenicol, and trimethoprim" (CDC).
Change of the targets or the antibiotic
Various antibiotic drugs aim a specific part to destroy and kill the whole body of bacteria. However, as the antibiotic resistance gene changes the antibiotic's target, the medication does not affect the bacteria, losing its function.
Beta-Lactam has a target to bind proteins that are found in the peptidoglycan layer of the bacteria. When the bacteria have a gene for changing the target of destruction, the Beta-lactam like penicillin cannot bind to the protein anymore because of the modification of the protein site.
The target change resistance strategy is used for the MRSA infection, methicillin-resistant staphylococcus aureus infection, "caused by a type of staph bacteria that has become resistant to many antibiotics.
Moreover, the Escherichia coli bacteria containing mcr-1 gene can add a resistant compound to the outside of the membrane to avoid the antibiotic attaching to the membrane and reaching the target to destroy
Destroy the antibiotic
Changing and destroying the antibiotic is performed with enzymes: catalyst and biological protein that breaks down the drug).
For instance, the Beta-lactam ring found in penicillin is an active, closed ring. However, when the Beta-lactam ring encounters the Beta-Lactamase in the bacteria, the enzyme which contains the multi-resistance to 𝝱-lactam antibiotics, the Beta-Lactam ring becomes inactive, which makes 𝝱-lactam antibiotics (penicillin, cephalosporins, etc) non-effective. Furthermore, the Klebsiella pneumoniae bacteria produce carbapenemases enzymes, breaking the antibiotic.
How to spread the antibiotic resistance gene between two bodies
Two possible solutions for the antibiotic resistance gene
(These are a few unverified solutions that I suggest)
Since the antibiotic resistance gene changes the antibiotic's target and uses an efflux pump in the bacteria to destroy, the antibiotic can contain a distractor, or the new antibiotic helper can be created as a distractor that confuses the bacteria’s ability to detect the antibiotic.
Create a system like an acid-base buffer that can resist the change of neutralization process by bacteria. The acid-base buffer can resist the pH change although strong base and acid enter the solution. The charge can use the buffer to resist the neutralization of the negative charge of the antibiotic, using the mechanism of pH, when the antibiotic resistance gene removes the effects of the antibiotic with the lipid membrane.
Work Cited Page
The Public Engagement team at the Wellcome Genome Campus. (2016, January 25). What is antibiotic resistance? Facts. https://www.yourgenome.org/facts/what-is-antibiotic-resistance.
Khondker, A., & Rheinstädter, M. C. (2020, February 17). How do bacterial membranes resist polymyxin antibiotics?Nature News. https://www.nature.com/articles/s42003-020-0803-x.
Centers for Disease Control and Prevention. (2020, February 10). How Antibiotic Resistance
Happens. Centers for Disease Control and Prevention. https://www.cdc.gov/drugresistance/about/how-resistance-happens.html.
Khan Academy. (n.d.). DNA cloning and recombinant DNA (video). Khan Academy. https://www.khanacademy.org/science/high-school-biology/hs-molecular-genetics/hs-biotechnology/v/dna-cloning-and-recombinant-dna.
MacLean, R. C., & Millan, A. S. (2019, September 13). The evolution of antibiotic resistance. Science. https://science.sciencemag.org/content/365/6458/1082/tab-figures-data.
Antibiotic resistance genes identified by researchers.
Drug Target Review. (n.d.). https://www.drugtargetreview.com/news/26760/antibiotic-resistance-genes-identified/.
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