🕒 6 min
Flashback to September 3, 1928. On an ordinary autumnal morning in foggy London, Alexander Fleming is returning to the Laboratory of St. Mary’s Hospital, ready to tackle the tasks he left before going on holiday. Firstly, quick and easy one- sorting the petri dishes, with, well, as Fleming thought, probably nothing interesting in them, just a bunch of life- threatening strains of bacteria that are currently killing millions of children and adults across the globe. But he was wrong, today was the day for “Eureka!”. On one dish was something unusual- it was dotted with colonies of growing bacteria, save for the one area where a blob of mold was growing. The zone immediately around the mold was clear, as if the mold had secreted something that inhibited bacterial growth. Today, we know that the mold was a rare strain of Penicillium notatum that secreted penicillin, very unstable substance at first, but many optimisations later, one of the greatest discoveries and advances in therapeutic medicine. The dawn of antibiotic era has begun.
Almost 100 years later, we are having it the other way around, facing the urgent health threat- antimicrobial resistance. In short, antimicrobial resistance (AMR) happens when germs, such as bacteria, parasites, viruses and fungi, change over time and develop the ability to defeat the drugs that are designed to kill them. In that manner, medicines become ineffective and infections persist in our body, increasing the risk of spread to others. Usually easily treated infections become so called resistant infections which are very hard, sometimes even impossible, to treat. Antimicrobials- including antibiotics, antivirals, antifungals and antiparasitics- are medicines used to prevent and treat infections in humans, animals and plants. Their uses are spread through healthcare, veterinary and agriculture industries. Therefore, antimicrobial resistance has the potential to affect people at any stage of life, what makes it one of the world’s most urgent health problems.
In order to find possible solutions for the problem, it is important to know about and understand all the mechanisms of antimicrobial resistance. So, how does antimicrobial resistance happen? Antibiotics are the class of drugs that fight bacterial infections, while antifungals/ antimycotics treat fungal infections. It is well known that both drug types save lives, but their use can also contribute to the development of resistant germs, also called “superbugs”. Antimicrobials are unfortunately not selective towards one strain of bacteria or fungi, which means they also kill helpful germs in our body that protect our body from infection. On the other hand, the growing concentration of antimicrobials on the infection site pressurises the infectious bacteria and fungi to adapt, which accelerates antimicrobial resistance. When they have successfully adapted, antimicrobial-resistant germs survive and multiply. The result is a resistant infection.
To adapt and survive, bacteria and fungi develop defence strategies against antibiotics and antifungals called resistance mechanisms. Their DNA carries the genes and codes for specific proteins, which then determine resistance mechanisms. Bacteria and fungi can carry genes for many types of resistance. The fact that different combinations of resistant mechanisms can occur in one microorganism makes all antibiotics or antifungals ineffective. Alarmingly, antimicrobial-resistant germs can pass on their resistance mechanisms on the other germs that haven’t been exposed to antibiotics or antifungals (in bacteria for example through conjugation, transduction or transformation). In the following table you can find a few examples of defence strategies used to resist the effects of antibiotics or antifungals.
|Restrict access of the antibiotic into the cell||Gram-negative bacteria (for example Escherichia Coli that causes urinal and many other infections or Pseudomonas aeruginosa that causes resistant pneumonia) have an outer membrane, a layer that protects them from their environment. They are a significant medical challenge as their outer membrane can selectively keep antibiotic drugs from entering the cell.|
|Get rid of an antibiotic or antifungal||Some Pseudomonas aeruginosa bacteria can produce pumps called porins, to get rid of several different important antibiotic drugs, including fluoroquinolones, beta-lactams, chloramphenicol and trimethoprim. Some fungal species such as Candida produce pumps that get rid of azole antimycotics such as fluconazole.|
|Change or break down the antibiotic||Klebsiella pneumoniae bacteria produce enzymes, proteins that break down the drugs, called carbapenemases. These enzymes break down carbapenem drugs and most other beta-lactam drugs, which makes the drugs ineffective.|
|Change the targets for the antibiotic or antifungal||Many antibiotic drugs are designed to single out and then destroy specific parts of bacterial cells. Escherichia coli bacteria with the mcr-1 gene can add a compound on the outside of the cell wall so the drug colistin cannot latch onto it. Aspergillus fumigatus fungi changes the cyp1A gene so that triazole antimycotics cannot bind to the protein.|
|Bypass the effects of the antibiotic||Germs develop new cell processes that avoid using the antibiotic’s target, like some Staphylococcus aureus bacteria can bypass the drug effects of trimethoprim.|
Another common cause of persistent infections is the formation of bacterial biofilms. Biofilms are clusters of microorganisms that stick to biological and non-biological surfaces, from epithelial cells in human body to plastic surfaces or rocks in a stream. Microbes form a biofilm in response to several stress factors, such as lack of nutrition and exposure to antibiotics. In a biofilm, highly complex and dynamic structure, bacterial cells stick to each other and function as a community. By producing different substances, cells can also communicate with each other through signal molecules, which are part of “quorum sensing”, a complex intracellular communication system. Thanks to quorum sensing, bacterial cells in a biofilm can exchange nutritional and other factors which can help them to survive in their environment. That is why bacterial biofilms are often called as “cities for microbes”. The biggest problem of a biofilm is that it can protect itself from high concentrations of antibiotics and bacteria can persist in our body, causing life-threatening infections that do not respond to any therapy.
To sum up, antimicrobial resistance has the potential to become one of the most problematic health threats of all time, if we do not take action. Addressing this threat requires continued aggressive action to prevent infections in the first place, improve antibiotic and antifungal use to slow the development of resistance and stop the spread of resistance when it does develop. To raise awareness of this global problem, the World Health Organization (WHO) celebrates World Antimicrobial Awareness Week (WAAW) from 18-24 November every year. Their priorities are to promote research and development of new therapeutic strategies, monitor AMR burden and response, lead global efforts and drive public health impact. No one can completely avoid getting an infection, but there are steps you can take to reduce the risk of infection and stop the spread of germs:
- Keeping Your hands clean is one of the best ways to avoid getting sick and prevent the germs from spreading.
- Vaccines are an important step to prevent most of the infections, including resistant ones.
- The use of antibiotics and antifungals appropriately is a huge step in the right direction. Nowadays, antibiotics or antifungals are unfortunately prescribed even when they are not needed. Another problem is that patients often stop taking the medicine way before the infection is supressed. When You get a prescription for an antibiotic, always use it the way your doctor or pharmacist has explained.
- Be aware of changes in Your health and talk to Your health provider about how to recognize signs and symptoms of infections, if you think you have an infection.
- Always clean Your hands after touching, feeding or caring for animals. Keep Your animals and pets healthy.
- Prepare food safely- separate raw meat from other foods, cook foods to safe temperatures, chill leftovers and other foods promptly.
- Stay healthy when traveling abroad. Know what vaccinations are needed, check health alerts, consume safe food and drinks, plan in advance in case you get sick and learn about the risks of medical tourism. (Source: www.cdc.com)
By following these easy steps, we have a chance of fighting the “superbugs”. What do you do to fight the antimicrobial resistance?