Penicillin was discovered in 1928 as a drug that kills bacteria. It took years of research before it could be mass-produced and made commercially available by 1945. Penicillin revolutionized the field of medicine and saved lives by killing the root cause of infectious diseases such as scarlet fever, pneumonia, syphilis, and other infections resulting from open wounds. Modifications to the chemical structure of penicillin led to the development of a class of penicillin-type antibiotics that are more effective against a wider range of infectious bacterial species. It has been less than a century since the discovery of penicillin, and now we see bacteria evolving to be resistant to antibiotics.
How do antibiotics work?
Bacteria are unicellular organisms. In most cases, bacteria survive in colonies where they exchange information via chemical signals. Antibiotics attack the parts or the functions of the bacteria that are responsible for their survival.
Disrupting cell walls: Some bacteria have cell walls that protect them against physical stress. Drugs like penicillin disrupt the cell walls and prevent their rebuilding. This causes the bacteria to swell up and ultimately burst. However, not all bacteria have a cell wall and they remain resistant to penicillin. It is important to know the kind of bacterial infection before treatment with penicillin.
Blocking essential functions: All living cells, including bacteria, have cellular machinery that produces and recycles complex molecules like proteins and nucleic acids. A certain class of antibiotics blocks the bacterial cell from performing these essential functions by binding to the machinery. Bacteria develop resistance to these antibiotics by actively pumping drugs out, producing chemicals that attack the drug itself, or changing the working of their machinery.
Leaking cellular content: Cell membranes are made of lipid bilayers that keep the aqueous interior of the bacterial cells from leaking out. Some antibiotics act like detergents, damaging the cell membrane. The bacteria rapidly lose important ions and molecules, leading to their death. Such antibiotics cause physical damage to the cell membrane. It is difficult to develop resistance to these antibiotics as it would require the bacteria to rebuild the entire cell membrane. Although this class of antibiotics is the last resort against antibiotic-resistant bacteria, some of these drugs are known to cause kidney problems.
Why is antibiotic resistance a global threat?
Antibiotic resistance is a result of evolution and natural selection. In all living systems, random mutations occur regularly. Some of these mutations have an advantage and function better than others in surviving. These mutations get passed on to further generations. Bacteria in large colonies also undergo similar mutations. Some of these mutations help them survive against antibiotics. Since bacteria have a short lifecycle, these mutations occur and are passed on very quickly to new generations, giving rise to "superbugs" that are resistant to almost all antibiotics. Bacteria also have a unique way of sharing pieces of genetic information with other members of the colonies. Consequently, the existing bacteria also develop resistance.
Misuse of antibiotics without identifying the causative bacteria, not completing the full antibiotic dose, and overuse of antibiotics in agriculture and livestock are major reasons leading to antibiotic resistance. Bacterial infections spread easily from one place to another via air, water, the food supply chain, and human travel. Antibiotic resistance is particularly problematic as it cannot be contained in one area and is a rising global concern.
Do we have an escape plan?
The rapid rise of antibiotic resistance is a race against time. Without new technology, we risk returning to a pre-penicillin world, where even minor cuts could result in deadly infections. Greater awareness is needed across hospitals, pharmacies, and educational institutions to ensure antibiotics are prescribed at the appropriate dose and duration, and only when clinically justified. Regulatory reforms are needed in countries where antibiotics are available over the counter, often at low doses. Without proper identification of the bacterial strain, such low doses risk prolonging illness and worsening its severity. Meanwhile, alternatives such as bacteriophages, which selectively destroy bacteria without harming human cells, and membrane-disrupting peptides are emerging as promising solutions.
All these approaches cannot eliminate the occurrence of antibacterial resistance, which is a natural process. We just need to slow the spread long enough for science to develop the next generation of treatments.
