Antibiotics – Handle them with care!

Antibiotics – Handle them with care!

Franz Schubert (1797 – 1828), Emily Brontë (1818 – 1848) y Henri de Toulouse-Lautrec (1864 – 1901)

 

What do Franz Schubert, Emily Brontë and Henri de Toulouse-Lautrec have to do with each other? All three died young due to diseases of bacterial origin that today are treated with antibiotics. The discovery of penicillin in 1928 by Alexander Fleming marked the beginning of the era of antibiotics. Many diseases that until then were incurable or difficult to treat ceased to be a threat. Mankind had found a way to fight against bacterial infections, but bacteria have been around for a long time and they also found a way to resist. Bottles of penicillin were comercialized around 1943 and a few years later the first cases of resistant Staphylococcus aureus were described. For years the problem was solved with the introduction of new antibiotics. However, the number of resistances continues to increase, while the procurement of new drugs is decreasing.

According to the World Health Organization (WHO) “Resistance to antibiotics is today one of the greatest threats to global health, food security and development.” If we don’t find a way to stop this threat there will be such an important regression in the treatment of infectious diseases that we could travel back to the time of Schubert, Brontë or Toulouse-Lautrec.

 

Image of a plate culturing bacteria from the Enterobacteriaceae family, really resistant to carbapenems (a type of betalactamic antibiotic).  Each disc contains an antibiotic and the surrounding growth inhibition halo defines whether the bacterium is resistant or sensitive to the antibiotic tested. Retrieved from: https://twitter.com/BriersYves/status/1086734750344187907

 

What does it mean that bacteria become resistant?

Resistance to antibiotics is an adaptation mechanism and can occur through two processes:

  • Mutation: Permanent change in the DNA of an organism, which in some cases make a bacterium resistant to a given antibiotic.
  • Horizontal gene transfer: Process whereby a bacteria transfers genetic information (DNA) to another individual which is not its descendant. Many antibiotics come from environmental microorganisms that do not have infectious capacity. Therefore, it is believed that the ability to resist certain antibiotics is a mechanism of said environmental bacteria to avoid being killed by their antibiotic. Over time, these resistances have reached pathogenic bacteria by horizontal gene transfer.
diana target objectiu antibiotic antibiòtic antibiótico mecanismes mecanismos resistencia resistencias bomba eliminar proteger expulsar impedir modificar enzima enzim enzyme modify betalactams betalacàmics betalactámicos resistències antibiòtiques adaptacions microbiologia unautes fàrmac
Sensible bacteria that can become resistant through mutations or horizontal gene transfer.

¿What are the main mechanisms of resistance?

A. Modifications of the target (point where the antibiotic acts):

1. Mutation of the target: The resistance to quinolones is due mutations in bacterial topoisomerases, the site where the quinolones act.
2. Enzymatic target modification: Resistance to vancomycin is obtained by a restructuring of the cell wall, preventing the action of the antibiotic.
3. Substitution of the target: Resistance to beta-lactams (such as penicillin) is sometimes due to the bacteria producing interfering proteins that binding to the antibiotic.
4. Protection of the target: Also in the case of resistance to quinolones, bacteria can produce proteins that protect the topoisomerases from the effect of the antibiotic.

diana target objectiu antibiotic antibiòtic antibiótico mecanismes mecanismos resistencia resistencias bomba eliminar proteger expulsar impedir modificar enzima enzim enzyme modify betalactams betalacàmics betalactámicos resistències antibiòtiques adaptacions microbiologia unautes fàrmac

B. Reduction of the antibiotic concentration:

1. Preventing the entry of the drug into the bacteria: Pseudomonas aeruginosa strains deficient for the imipenem transporter are resistant to this drug.
2. Extracting the antibiotic through flow pumps: The flow pumps move compounds through the wall of the bacteria and are not always specific for a type of substrate, but sometimes transport a wide range of compounds of similar structure, including many classes of antibiotics.

diana target objectiu antibiotic antibiòtic antibiótico mecanismes mecanismos resistencia resistencias bomba eliminar proteger expulsar impedir modificar enzima enzim enzyme modify betalactams betalacàmics betalactámicos resistències antibiòtiques adaptacions microbiologia unautes fàrmac

C. Antibiotic modification:

1. Through modifications in the enzyme responsible for activating the pre-antibiotic: isoniazid is an antibiotic that acts through the catalase enzyme produced by bacteria. In Mycobacterium tuberculosis, resistance to isoniazid is achieved by reducing the activity of catalase.
2. Presence of enzymes that inactivate the antibiotic: The resistance of Staphylococcus aureus to penicillin is due to the transmission of plasmids that code for penicillinase, enzymes that destroy this antibiotic.

diana target objectiu antibiotic antibiòtic antibiótico mecanismes mecanismos resistencia resistencias bomba eliminar proteger expulsar impedir modificar enzima enzim enzyme modify betalactams betalacàmics betalactámicos resistències antibiòtiques adaptacions microbiologia unautes fàrmac

And what does that imply? What can be done to prevent it?

According to the CDC, every year 2 million people in the US suffer from an infection due to antibiotic-resistant bacteria, and 23,000 people die from this infection. The uncontrolled use of antibiotics is accelerating the emergence of resistances that can be a major threat. But not all is lost. WHO proposes a series of measures to prevent and control the spread of antibiotic resistance. Among them, the most important measures are the following:

  • Do not self-medicate, take antibiotics only when a certified health professional tells you. Know that not all infectious diseases are cured with antibiotics and that not all are good for everything.
  • Follow the treatment instructions and finish it. An unfinished treatment can cause the bacteria responsible for the infection not be completely eliminated and develop a resistance, and may produce a worse infection later.

Therefore, as indicated by this poster of the WHO, antibiotics must be handled with care.

Poster of the 2017 campaign for awareness of the use of antibiotics. Retrieved from: https://www.who.int/campaigns/world-antibiotic-awareness-week/2017/posters/en/

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888801/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603022/pdf/12915_2017_Article_423.pdf
https://www.ncbi.nlm.nih.gov/pubmed/24847651
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154455/
https://www.who.int/campaigns/world-antibiotic-awareness-week/2017/posters/es/
https://www.cdc.gov/drugresistance/about.html
https://www.who.int/es/news-room/fact-sheets/detail/resistencia-a-los-antibi%C3%B3ticos
https://www.investigacionyciencia.es/files/26371.pdf

Leave a Reply

Your email address will not be published. Required fields are marked *