This is the first installment of an ongoing series. For installment two, visit here.
By: James Peacock
Antibiotic resistance, or the ability for pathogens to evolve to the point where an antibiotic is unable to properly function against it, is an issue that has grown in size exponentially over the last few years. As we move into the future, measures will need to be taken in order to curb the spread of antibiotic resistance, or we may lose the effective antibiotics that we have developed over the years. But what are antibiotics anyway? How do they work? When did they come about? In this, the first installment in our series on Antibiotic Resistance, we will go over the basics of antibiotics, as well as the recent development of antibiotic resistance.
The History of Antibiotics
The history of antibiotics really begins with the history of humanity. Scientists have been able to find traces of antibiotic usage since ancient times, but this was more than likely the result of luck. People in ancient times had no practical understanding of disease, so any antibiotic use would be most likely coincidental. The antibiotic era as we know it began in the early 20th century. Scientists and researchers had been experimenting with chemicals for some time in an effort to find a combination that would inhibit the growth of bacteria. While there were some early successes, the medications created by these experiments were expensive and hardly effective. The first major breakthrough in antibiotic research came in 1928. On September 3, 1928, a Scottish scientist named Alexander Fleming was working with penicillium and accidentally discovered that the cultures he produced had antibiotic properties. From this, he was able to isolate benzylpenicillin – the world’s first antibiotic.
Penicillin would not be mass produced until 1945, but once it was it had an instant impact on the general health of society. Doctors now had an effective medication for dealing with an issue that had confounded them just a few years prior. As such, doctors began to prescribe the new antibiotics for a myriad of illnesses. This led Fleming himself to warn about potential resistance, but this warning would go largely unheeded. From the 1950s to the 1970s, scientists continued to discover new antibiotics, leading to the foundation of several classes of antibiotic. After this time period, however, new antibiotics became hard to manufacture. There has been a sharp downturn in the amount of new classes of antibiotics discovered since this era, which is another contributing factor for antibiotic resistance.
There are currently 9 different classes of antibiotics. The first is the Beta-Lactam antibiotics, which was the first class discovered. Penicillin and cephalosporin are examples of antibiotics from this class, as both have the beta-lactam molecular structure that makes this class unique. Second are the tetracyclines, named for the 4 carbon rings commonly found in these chemicals. These antibiotics are typically used for infections of the skin, although they can be effective against Listeria monocytogenes. Macrolide antibiotics make up the third class. Also named for their shape, these antibiotics are used for everything from respiratory tract infections to skin diseases. Class 4 antibiotics are known as Aminoglycosides. These antibiotics, of which Gentamicin, Streptomycin, and Amikacin are examples, are a class that are effective against most bacteria that have yet to develop resistance. This class was also important historically, as streptomycin was the first successful antibiotic used against tuberculosis. The fifth class is known as Quinolones. These synthetic antibiotics are typically used to treat infections that are believed to be resistant to older antibiotics. The sixth class of antibiotics, known as cyclic peptides, are complex antibiotics that have a predictably circular structure. Members of this group, including bacitracin, colistin, and nisin, have a myriad of uses. Lincosamides make up the 7th class. Mainly made up of lincomycin and clindamycin, these antibiotics can also be effective against protozoa, as well as diseases such as malaria. Class 8, known as Oxazolidinones, are used to treat pneumonia. The last class, sulfa antibiotics, are not as widely used. This is due to the prevalence of sulfa allergies in society, as well as more powerful antibiotics.
How Antibiotics Work
Antibiotics are used to eliminate bacteria. They can do this in quite a few ways, but almost all disrupt the bacteria’s ability to survive and reproduce. Hardly any antibiotics physically kill the bacteria. Instead, they cause damage in other ways. For example, Lincosamides work by stopping the synthesis of some proteins. Bacteria use proteins like any other living thing, and rely on ribosomes (or protein-making parts in the cell) to create them. Without some of the proteins blocked by Lincosamides, the bacteria will be unable to reproduce, thus halting the infection. Lincosamides themselves are incredibly useful, as they disrupt the ribosomes of bacteria, but not humans. This is because the structure of human ribosomes is different from bacteria. Several other classes of antibiotics also work to inhibit protein synthesis, but there are other ways to stop a bacterial infection. One of these ways is used by the Quinolone class. These antibiotics do not target ribosomes, but rather a specific enzyme called topoisomerase II. This enzyme separates DNA during the DNA replication process. The DNA replication process creates a copy of the DNA in a cell so that when the cell reproduces, both cells can have the same DNA. By modifying the topoisomerase, Quinolone antibiotics can cause DNA fragmentation, which makes it impossible to replicate. Some antibiotics, such as Aminoglycosides, can do more than one thing. Not only do Aminoglycosides disrupt the synthesis of proteins in bacteria, but they can also cause a breakdown in the cell membrane. If the cell membrane is lost, then the bacteria dies.
How Antibiotic Resistance Works
Antibiotic resistance is simply the work of natural selection. Bacteria reproduce rather quickly, so it is easy for multiple generations to exist at one time. With each new generation, random mutations take place, sometimes resulting in new processes for the cell. These mutations are usually the result of mistakes made during the replication process or from exposure to chemicals in the environment. If a bacteria is repeatedly exposed to chemicals, it may end up developing a way to combat that chemical. For instance, penicillin may be used to combat an infection. One of the bacteria has a genetic mutation that allows it to resist penicillin, so it survives the dose of antibiotics. This bacteria will reproduce, and now you have an antibiotic resistant infection. In fact, this happens more and more often with penicillin and other antibiotics that have been used for a long time.
As antibiotics continue to be used in ever increasing amounts, the amount of antibiotic resistance will increase. And in many cases, bacteria have successfully developed resistance to antibiotics. While this is an issue that has been growing for decades, it is only recently that antibiotic resistance has been considered a global health issue. This is mainly due to the development of the mcr-1 gene. The mcr gene, and how health officials have responded to growing resistance, will be covered in part 2 of this series. Stay tunes for our next installment.