Kc obtained his Bachelor of Science in Biochemistry and is passionate about all things pertaining to biochemistry.
Before the advent of penicillin, there was no treatment for infections such as gonorrhea, pneumonia, and rheumatic fever. Doctors could not do much for patients with these infections but wait and hope, and pray that their patients survived. But then, as fate would have it, a scientist by the name of Alexander Fleming chanced upon a discovery that would change the practice of medicine forever.
In 1928 Fleming was sorting through Petri dishes containing colonies of Staphylococcus when he noticed something peculiar. In one of the Petri dishes, he spotted a moldy growth. What was interesting about this growth was that the area around it was free of bacterial colonies. It was as if the mold had secreted a substance that inhibited the growth of the bacteria. Fleming would later discover that the substance was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus, and the diphtheria bacillus. He immediately set out to isolate this mystery substance with his assistants, Stuart Craddock and Frederick Ridley, but their attempts at isolation were unsuccessful.
It was only when Howard Florey and his colleague Ernst Chain began experimenting with mold cultures in 1939 that penicillin was successfully isolated, and in 1941 they treated their first patient with penicillin. Ironically enough, when Alexander Fleming received his Nobel Prize for his work on penicillin, he used his acceptance speech to warn of the dangers of bacteria becoming resistant to the “miracle drug.” Almost a century later, his warning seems to be turning into reality as penicillin and many other drugs like it are in danger of becoming obsolete with the rise of antibiotic resistance.
What are Antibiotics?
Antibiotics are naturally occurring or artificially synthesized drugs that kill bacteria or inhibit their growth. They do this by specifically targeting structures or processes that differ in bacteria or are absent in humans. For example, some antibiotics prevent the development of the cell walls of bacteria (human cells lack cell walls), others attack their cell membrane which differs in structure from human cells, and a select few attack their DNA-copying and protein-building machinery.
The cell walls of bacteria add rigidity and prevent the cells from rupturing under their own pressure. These cell walls are synthesized by the action of penicillin-binding protein. A group of antibiotics called Beta-lactams work by inhibiting penicillin-binding protein. By inhibiting penicillin-binding protein Beta-lactams prevent the synthesis of bacterial cell walls. Without support from their cell walls, the pressure within bacterial cells causes their cell membranes to rupture, which spills their cell contents into their surroundings, killing the bacterial cells in the process.
Ribosomes help make proteins by reading mRNA and linking amino acid to form a peptide chain. Ribosomes are present in both bacteria and human cells, but their structure differs. Macrolides work by binding to the ribosome of bacteria and inducing the disassociation of tRNA, which prevents the synthesis of proteins. Proteins perform a host of functions including maintaining cell shape, cleaning up waste, and cell signaling. Since proteins do all of the cell’s work, inhibition of protein synthesis causes cell death.
Quinolones work by disrupting the DNA replication process. When bacteria begin to copy their DNA, quinolones cause the strand to break and then prevent their repair. Without intact DNA, bacteria cannot synthesize many of the molecules they need to survive, and so by disrupting DNA replication quinolones succeed in killing bacteria.
How do Bacteria Acquire Antibiotic Resistance?
Bacteria acquire antibiotic resistance in one of two ways: through mutations or transfer of DNA.
1. Gene Mutations
Gene mutations occur at random. Some mutations are harmful, and some mutations don’t change the structure and function of the protein they code for, but others may give an advantage to the organism that possesses it. If a mutation changes the structure of a protein at the site of antibiotic binding, then the antibiotic can no longer bind to that protein. Such a change prevents the antibiotic from performing its function and so the bacterium is neither killed nor is its growth inhibited.
2. Horizontal Gene Transfers
Horizontal gene transfer between bacterium occurs via three mechanisms: transformation, conjugation, and transduction.
When a bacteria dies it may lyse and spill its contents, which include DNA fragments, into their surroundings. From there other bacteria may take in this foreign DNA and incorporate it into their own DNA. In the process of doing so, it acquires the characteristics coded for by that DNA fragment. If by chance the DNA fragment codes for resistance to an antibiotic and is taken up by a susceptible bacterium then that bacterium “transforms” and becomes resistant as well.
Some bacteria have small pieces of circular DNA (plasmids), separate from their primary chromosome, sitting freely in their cytoplasm. These plasmids can carry genes that code for antibiotic resistance. Bacteria with plasmids can perform a mating process called conjugation, in which replicated plasmid DNA is passed from donor bacterium to recipient bacterium. If the plasmid happens to contain a gene that codes for resistance to an antibiotic, then the recipient bacterium becomes resistant to that antibiotic.
Bacteriophages are small viruses that infect bacteria and hijack their DNA replication, DNA transcription, and DNA translation machinery to produce new bacteriophage particles. During this process, bacteriophages may take up host DNA and incorporate it into their genome. Later on, when these bacteriophages infect a new host, they may transfer the DNA of their previous host into the new host genome. If this DNA happens to code for antibiotic resistance, then the host bacterium becomes resistant as well.
How Does Antibiotic Resistance Spread?
When antibiotics are used, resistant strains of bacteria have higher survival rates than susceptible bacteria. Frequent use of antibiotics over a long period of time puts selective pressure on the population for the survival of resistant strains of bacteria. With fewer bacteria around to compete for space and food, resistant bacteria begin multiplying and pass on their resistant trait to their offspring. Eventually, with time the population of bacteria becomes composed of mostly resistant strains.
In nature, some bacteria are capable of producing antibiotics to use against other bacteria. So even in nature, in the absence of antibiotic use by humans, there is selective pressure to pass on resistance. So why is this process important?
Well, because farmers routinely give their animals antibiotics to make them grow faster or help them survive crowded, stressful, and unsanitary conditions. Using antibiotics improperly in this way—to boost productivity, not to fight infections— kills susceptible bacteria but allows resistant bacteria to survive and multiply.
Strains of bacteria that are resistant to antibiotics end up in the guts of animals. From there, they can be excreted in feces or passed on to humans when contaminated animals are slaughtered and sold as meat products. If contaminated meat is not handled or prepared properly, resistant strains of bacteria can infect humans. On the other hand, contaminated animal feces may be used to produce fertilizer, or they may contaminate water. The fertilizer and water may then be used on crops contaminating them in the process. When these crops are harvested and sent to markets to be sold, antibiotic resistant bacteria are brought along for the ride. Humans who eat crops contaminated with resistant strains of bacteria become infected with that bacteria and may, in turn, infect other humans.
On the other end of this spectrum, the use of antibiotics by humans, as with animals, may result in the development of antibiotic resistant strains of bacteria in their gut. Infected humans may then stay in their communities and infect other humans, or may seek medical attention at a hospital. There the host can unknowingly spread antibiotic-resistant bacteria to other patients and healthcare workers. Patients may then go home and infect other individuals with resistant strains of bacteria.
Another concern is that people can obtain some antibiotics without a prescription that they'll routinely use to treat viral infections such as colds and sore throats, even though antibiotics have no effect on viruses. Misuse of antibiotics in this way also speeds up the spread of antibiotic resistance.
Lately, it has become increasing difficult to treat patients now that there are more resistant strains of bacteria. Penicillin, which used to be the go-to drug to treat infections, is now becoming ineffective. If this trend continues, all current antibiotic drugs could become ineffective in the next few years.
Where Do We Go From Here?
The Centers for Disease Control and Prevention (CDC) estimates that approximately over 2 million reported cases of illnesses and 23,000 deaths are caused by antibiotic resistance in the U.S. alone. Globally, antibiotic resistance kills 700,000 persons per year, with this figure expected to reach millions in the coming decades. In light of this growing threat, the CDC has outlined four core actions to combat antibiotic resistance: preventing infections, tracking, improving antibiotic prescribing and stewardship, and developing new drugs and diagnostic tests.
Preventing infections will reduce the use of antibiotics for treatment, and this will reduce the risk of antibiotic resistance developing. Proper food handling, proper sanitary practices, immunization, and strictly adhering to the guidelines of an antibiotic prescription are all ways to help prevent antibiotic-resistant infections. The CDC is tracking the number and causes of drug-resistant infection so that they can develop strategies to prevent those infections and prevent antibiotic resistance from spreading. Improved antibiotic prescribing and stewardship can significantly reduce the exposure of bacteria to antibiotics and can reduce the selective pressure for antibiotic resistance.
In particular, the unnecessary and inappropriate use of antibiotics by humans and in the rearing of animals creates scenarios in which antibiotic resistance can arise. Phasing out these two will help to slow down the spread of antibiotic-resistant strains of bacteria.
Antibiotic resistance, although it is a cause for concern, can only be slowed, not stopped, because it is a part of the bacteria’s natural process of evolution. Therefore what is necessary is the creation of new drugs to fight bacteria that have grown resistant to older drugs.
The National Resources Defense Council (NRDC), aware of the ongoing crisis, has been pushing for food companies to reduce the use of antibiotics in their supply chains. Recently, the fast food giant McDonald’s has announced its goal of phasing out the use of chicken that has been raised with antibiotics within two years. Other companies like Chick-Fil-A, Tyson, Taco Bell, Costco, and Pizza Hut have pledged to do the same in the upcoming years.
Even though the announcement by McDonald’s comes as great news, the company is only committed to phasing out antibiotic-grown chicken, not beef or pork. However, since McDonald’s is one of the major competitors in the fast food business, its announcement to phase out chicken grown with antibiotics will no doubt influence the decisions of other restaurants and the production of other meats.