Drug Treatment Resistance Explained: Why Some Drugs Stop Working
“When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.”
—Alexander Fleming
Alexander Fleming wasn’t being modest. When he returned from summer vacation to his lab at St. Mary’s Hospital in London, he found that Penicillium notatum had contaminated his lab cultures of Staphylococcus aureus and — to his surprise — stopped the bacteria from growing.
That unexpected finding marked the beginning of antibiotics: powerful medicines that kill bacteria while leaving human cells unharmed.
Before antibiotics, everyday life was far more dangerous. A cut, graze or puncture — any break in the skin — could turn deadly. Medical procedures carried much higher risk, and at the turn of the 20th century, the three leading causes of death were all infectious diseases later treated with antibiotics.
Now, drug resistance threatens to erase nearly a century of progress. But what is drug resistance, and how do we combat it?
What Is Drug Resistance?
Drug resistance, also called antimicrobial resistance, occurs when microorganisms — like bacteria, viruses and fungi or even cancer cells — develop the ability to withstand treatment. Resistance can exist before treatment or develop after exposure to a drug.
Bacterial resistance to antibiotics gets the most attention, but many types of pathogens can evolve to resist medications, including:
- Antivirals
- Antifungals
- Antiprotozoals
How Does Drug Resistance Develop?
Antimicrobial resistance forms through natural selection, a process that removes organisms that cannot adapt to changing conditions and favors those that can.
Imagine this: A course of antibiotics or antifungals is prescribed and wipes out nearly all of the invading germs. But a few survive. Within that small group, some germ cells carry random genetic mutations that make them immune to the drug. These survivors multiply, spreading their resistant traits through their DNA to other germs.
Germs can even share resistance mechanisms with other germs that haven’t been exposed to the antibiotic or antifungal. Viruses that infect bacteria, called phages, can carry DNA from germ to germ, helping resistance move through microbial communities.
Chemotherapy Resistance
Cancer drug resistance is a major reason treatments stop working, and there are multiple mechanisms behind this failure, driven by both genetic and nongenetic factors.
Common resistance mechanisms in cancer include:
| Reduced drug uptake | The drug has less access to or effect on its intended target. |
| Drug efflux | Cancer cells pump out the drug before it can work. |
| Target alteration | The drug’s molecular target changes so the drug no longer binds effectively. |
| Blocked cell death | Cancer cell death pathways are inhibited, letting cells survive. |
| Enhanced DNA repair | Cancer cells fix drug-induced damage faster than the drug can cause it. |
| Cell heterogeneity | Tumor diversity means some resistant cells are always present to survive treatment. |
Because several resistance mechanisms can act at the same time, oncologists often use combinations of treatments and targeted strategies (such as surgery, radiation therapy, chemotherapy and newer targeted or immunotherapies) to improve outcomes and delay or overcome resistance.
Cancer remains a devastating illness, but advances in pharmaceutical research and cancer care mean that, for many patients, it’s no longer a death sentence.
Why Treatment Resistance Is a Crisis
In the United States, over 2.8 million antimicrobial-resistant infections occur every year, leading to more than 35,000 deaths. Infections caused by resistant germs are often extremely difficult, and sometimes nearly impossible, to treat. Globally, bacterial antimicrobial resistance is directly responsible for about 1.27 million deaths each year.
Often referred to as a “silent pandemic,” antimicrobial resistance is one of the top global public health crises.
What Are the Mechanisms of Drug Resistance?
Much like cancer cells, germs resist treatment through several types of mechanisms:
- Blocked entry: The germ blocks the antibiotic from entering the cell.
- Efflux pumps: The germ pumps the antibiotic or antifungal out of the cell.
- Drug inactivation: The germ changes or destroys the antibiotic so it no longer works.
- Target alteration: The germ modifies its own targets inside the cell so the drug can’t bind.
- Pathway bypass: The germ finds an alternate route around the pathway that the antibiotic is designed to block.
Antibiotic Resistance Causes: What’s Driving the Crisis?
Misuse is a major driver of antibiotic resistance. Antibiotics, which do not work against viruses, are often prescribed for colds, upper respiratory tract infections and bronchitis: illnesses that are almost always caused by viruses, not bacteria.
Alexander Fleming himself was one of the first to warn of the dangers of overuse. “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism,” he cautioned. “I hope the evil can be averted.”
Become Part of the Solution
The rise of resistant bacteria threatens to undo decades of medical progress. At the same time, pharmaceutical scientists are expanding our understanding of antibiotics and related therapies, working every day to develop and deliver new, more effective treatments.
If you want to contribute to this effort, you can do more than simply use antibiotics responsibly. The University of Florida offers several online medical sciences graduate programs designed to introduce you to drug discovery, development and clinical use, including:
- Master of Science in Medical Physiology and Pharmacology
- Graduate Certificate in Medical Pharmacology and Therapeutics
Antimicrobial resistance is one of the biggest public health challenges facing the planet. Whether you want to become a pharmaceutical scientist or a medical professional who prescribes medications responsibly, you can help address the antibiotic resistance crisis. A strong foundation in medical physiology, pharmacology and therapeutics is a good place to start.
Learn about UF’s medical sciences programs.
Apply to UF’s medical sciences programs.
Sources:
https://www.ncbi.nlm.nih.gov/books/NBK513277/
https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00118
https://www.ebsco.com/research-starters/health-and-medicine/drug-resistance
https://www.cdc.gov/antimicrobial-resistance/about/index.html
