How do Antibiotics work?

Just recently I saw an article about the misuse of antibiotics in the US and had a conversation with my housemate (who’s a doctor) about the use of antibiotics in modern society. I think there is a bit of controversy around the use of antibiotics, particularly when it comes to the meat and dairy industry, giving antibiotics a quite negative reputation. To shed some light on the value of antibiotics, I’ll start off with some basics on antibiotics, followed by some sentences on their importance, misuse and use in a research setting.

Antibiotics work only for bacterial infections, not viral infections, and can be subdivided based on their action mechanism – how they ‘injure’ bacteria and stop them from growing any further. The key point is that antibiotics target pathways and mechanisms exclusively found in bacteria, otherwise we would be harming our own, mammalian cells. The three most prominent action mechanisms interfere with bacterial:

  1. The cell wall synthesis
  2. Nucleic acid synthesis
  3. Protein Synthesis

A) The cell wall is like the protective skin of a bacteria, and additionally functions in transporting molecules from the outside the bacteria needs. If this structure is interrupted, the bacteria loses its osmotic gradient and basically erupts, resulting in its death.

B) Nucleic Acids are the basic building blocks for the DNA double helix – the genetic material. If this synthesis process is inhibited, the bacteria can’t replicate, proteins can’t be expressed, and bacteria cease to live.

C) Proteins are synthesized by ‘reading’ the genetic material (DNA) and translating the contained information to functional proteins that are required for maintaining a healthy bacterium. If this is interrupted, effects are similar to B), where the bacteria can’t maintain normal functions and dies.

There are additional antibiotics that target the synthesis of other specific molecules in bacteria, required for its survival, but constitute a much smaller class of antibiotics.

The sketch below nicely summarizes these action mechanisms:

Source: https://www.orthobullets.com/basic-science/9059/antibiotic-classification-and-mechanism

The probably most famous class of antibiotics are the penicillins, which were (accidentally) first discovered in the late 1920s by Alexander Flemming. Related drugs to penicillins, such as amoxycillin, are commonly prescribed to treat bacterial infections today. With increasing resistance development however, the different classes of antibiotics are becoming increasingly inefficient in treating infections – and with that our main weapon against bacterial infections is sinking.

The issue with widespread (mis)use of antibiotics is the development of resistances, as bacteria also constantly evolve and mutate. This evolution process enables the small number of bacteria that are resistant to the antibiotic action mechanism (due to spontaneous mutations) to survive and proliferate. If we wouldn’t “misuse” antibiotics, there wouldn’t be this human made ‘selection’ pressure, and resistance development would be much slower. With misuse I mainly refer to excessive, unnecessary use of antibiotics and inadequate consumption of these (e.g. taking them 4 days, although they were prescribed for 10, thereby not following through with the intended treatment). There are many other, perhaps more significant factors that contribute to resistance development, including overuse of antibiotics in livestock and associated produce. However, the above-mentioned issues are the ones we can personally influence quite easily.

Antibiotics in the Lab

In research the use of antibiotics is quite different than in society. It is quite common to use antibiotics as selection markers – a strategy to detect which cells were successfully genetically modified, as only modified cells will be resistant to the antibiotics, and all other non GMOed cells will die.

This is achieved by incorporating DNA which gives rise to resistance along with the actual DNA of choice on a circular plasmid (a type of genetic material that can easily be put into bacteria). This way, when the bacteria is resistant to the respective antibiotic, the DNA of choice was very likely also integrated into the bacterium. An example of such plasmid structure is shown below: The Red string is the DNA of choice to be integrated into the bacteria, while the blue part is the antibiotic resistance marker. The other parts are required for adequate expression of the inserted gene (in red).

Source: https://www.cfgenetherapy.org.uk/blog/article/Minicircle_v_Plasmids_Time_to_think_again

The use of antibiotics in research is incredibly valuable and allows simple and fast genetic modulation for research purposes. For treatments of bacterial infections in humans, antibiotics are also extremely important, however their widespread use has made their consumption somewhat “common”, resulting in the wake of antibiotic resistances becoming a healthcare crisis. Ultimately, one thing everyone can impact is the mindful intake of antibiotics when it comes to personal use.

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