Imagine getting up one morning with a sore throat and thinking to yourself: “Oh no, I just had a throat infection two weeks ago. I can’t believe it’s back!”. You promptly return to your two-week-old prescription and start the antibiotics your doctor previously gave you. Two days go by, but your throat infection doesn’t seem to be getting any better, so you start wondering, “How is it possible that after being on antibiotics for two days, I still feel sick?” What you’re experiencing is a case of antibiotic resistance. Basically, your throat infection refuses to improve because the bacteria responsible for the infection have become stronger and more resistant to the specific antibiotics you’re taking. Considering how frequently this happens, let’s try to understand this annoying situation a bit better.
Human Life and Pathogens
As a normal part of life, we’re all constantly exposed to an astounding number of pathogens – the tiny microbes and viruses that make us sick. In fact, scientific literature lists about 1,400 species of human pathogens, including 538 bacteria, 317 fungi and 208 viruses, among others. These pathogens are out there for one reason—to make us sick!
Who is protecting us from these savages?
Our good old immune system is the all-time savior from these disease-causing and potentially deadly organisms. During a bacterial attack, the bad bacteria release toxins to make us sick and our immune system kicks into action. As a result of the fight our body puts up, we develop a fever, rash, allergic symptoms, pus etc., all of which indicate that our immune system soldiers are working hard! Sometimes, however, our immune system is not triggered into action quickly enough and the bacteria win the battle. It also sometimes happens that the bacteria produce toxins so rapidly that our immune system is weakened and overpowered by the aggressive bacteria.
Antibiotics to the rescue!
Now, when our immune system gives up, we typically turn to antibiotics. Antibiotics are drugs, taken orally or injected, that kill or stop the growth of microorganisms. They are like magic bullets that interfere in the life processes of pathogens. They inhibit the growth of pathogens through one of the following mechanisms:
- Inhibiting the synthesis of the bacterial cell wall.
- Inhibiting bacterial protein synthesis.
- Inhibiting bacterial DNA replication.
- Inhibiting folic acid metabolism.
Antibiotic resistance – a global crisis!
When you keep using antibiotics indiscriminately, bacteria will develop the ability to fight the very drugs meant to kill them. The antibiotics will no longer be efficient in stopping bacterial growth, so bacteria will emerge stronger and more resistant to the medication. Think of antibiotics as a battlefield for notorious bacteria, where weak and susceptible bacteria perish. However, some bacteria emerge stronger and replicate even faster after coming in contact with antibiotics against whom they have already devised some survival strategies. The rapid emergence of resistant bacteria is occurring worldwide, seriously endangering the efficacy of antibiotics.
The History and Evolution of Antibiotic Resistance
Penicillin was the first antibiotic discovered by Sir Alexander Fleming in 1928. Since its discovery, penicillin was heavily used to treat soldiers suffering from bacterial infections during the Second World War. However, by the 1950s, penicillin resistance became a grave problem. This led to the development of beta-lactam antibiotics, but unfortunately, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was identified during the 1960s. Vancomycin, another antibiotic, was introduced in the 1970s to tackle MRSA, but that also showed resistance by the 1980s. Hence, many decades after the miraculous discovery of antibiotics, in our current day and age, we seem to have returned to a pre-antibiotic era due to the exponential rise of antibiotic resistance.
We understand very clearly now that antibiotic resistance is a “real” threat and a global cause of concern. Now, let’s look at the possible causes and mechanisms by which this resistance develops.
Causes of antibiotic resistance
- Inappropriate prescriptions in terms of the choice of antibiotic prescribed or an incorrect recommended duration of antibiotic therapy can both lead to the emergence of resistant strains of bacteria.
- Overuse of antibiotics –Following its introduction in the United States in the 1950s, penicillin was made available over the counter (OTC) for almost 10 years before prescriptions were required. Therefore, it is fair to say that a “core” population of antibiotic-resistant strains was established as early as the 1960s. In some countries, even today, antibiotics are available as OTC drugs and do not require a prescription. As a result, every time someone feels slightly sick, they pop an antibiotic pill without proper medical supervision, which leads to resistance.
How do bacteria become resistant to antibiotics?
Think of a bacterial cell as a fort or a castle, while antibiotics are soldiers of the invading army that are attacking the fort (bacterial cell). Forts and castles are known for having huge walls to prevent their enemies from entering the fort. In this case, the bacterial cell wall is representative of these fort walls and undergoes certain changes to stop the entry of antibiotic molecules into the bacterial cell. However, what actually happens when antibiotics are repeatedly administered?
Decrease in porin channels
Some antibiotic molecules can enter a bacterial cell only through “porin” channels present in the outer membrane of the bacterial cell wall. A decrease in the number of porin channels leads to the decreased entry of antibiotics into the cell, thus leading to the development of resistance to these antibiotics.
These pumps flush out the antibiotics from the bacterial cell before they reach their targets, making the bacteria resistant to that particular antibiotic.
Modification of the target molecule
Antibiotics usually bind to specific target sites in a bacterial cell. Natural variations or acquired changes in these target sites is a common mechanism of resistance.
Bacterial cells produce three main enzymes that inactivate antibiotics. These enzymes are β-lactamases, aminoglycoside-modifying enzymes, and chloramphenicol acetyltransferases.
How is antibiotic resistance becoming such a widespread phenomenon?
Horizontal gene transfer (HGT)
Bacteria are very good at sharing genes, including genes for antibiotic resistance. This form of horizontal gene transfer (HGT) enables antibiotic resistance to be transferred among different species of bacteria.
Transfer through livestock
Antibiotics are widely used as growth supplements in livestock to improve the overall health of the animals, and for producing larger yields. Antibiotic use in food-producing animals kills or suppresses susceptible bacteria, allowing antibiotic-resistant bacteria to thrive. These resistant bacteria are transmitted to humans through the food supply, which then increases the risk of infections in humans.
Why should you worry about antibiotic resistance?
We’re already in a day and age where antibiotics have stopped being effective against deadly infections, which in itself is a scary thought to live with. Many public health organizations have started using words like “nightmare scenario” to describe the current state of antibiotic resistance. Multi-drug resistant (MDR) bacteria are on the rise and pose a dire threat to all of us, as these bacteria remain unaffected by more than one antibiotic. Two common examples of MDR infections are methicillin-resistant Staphylococcus aureus (MRSA) and the drug-resistant M. tuberculosis infection. You might be shocked to learn that MRSA kills more Americans each year than HIV/AIDS, Parkinson’s disease, emphysema, and homicide combined!!! Tuberculosis (TB) is generally treatable and curable with drugs, but in the case of drug-resistant TB, the treatment can be more complex, including more side effects and a much higher cost.
Rise of the “superbugs”
A superbug is a strain of bacteria that has become resistant to antibiotics. An Antibiotic Threats Report released in 2013 listed some of the bacteria that are considered “urgent threats”. These include:
- Clostridium difficile, which causes life-threatening diarrhea, mostly in people who have undergone recent medical care or hospitalization.
- Carbapenem-resistant Enterobacteriaceae (CRE), also called nightmare bacteria. Carbapenems are antibiotics that are typically used when all other antibiotics fail. CREs are resistant even to carbapenems, which is quite terrifying.
- Drug-resistant Neisseria gonorrhoeae.
If the situation is so grim, what are we doing to deal with it?
According to the World Health Organization (WHO), the following measures can be taken by patients to handle this problem better.
- We should use antibiotics only under proper medical supervision and prescription.
- We should avoid using antibiotics for cold and flu, which are viral infections and therefore not affected by antibiotics. If we use antibiotics for viral infections, we add to the overall risk of antibiotic resistance.
- We should refrain from sharing our leftover antibiotics with others or repeating a particular prescription without medical guidance.
When antibiotics were discovered in the 20th Century, they were considered wonder drugs that would free us from all infections. However, with the passage of time and the overuse of these antibiotics, we now understand that the bacteria became smarter, meaning that we are now moving towards a post-antibiotic era. Therefore, we have to practice the judicious use of antibiotics or else face adverse health consequences at the hands of these antibiotic-resistant bacteria!