If you think that killer plagues and superbacteria are the stuff of horror movies alone, you may need to think again. Overuse and misuse of antibiotics have promoted the proliferation of antibiotic-resistant organisms. Antibiotics commonly used to kill pathogenic bacteria are now becoming ineffective and opening the way for potentially real and imminent danger.
When Alexander Fleming first discovered penicillin in 1929, it was touted as a miracle drug, and at the time it was. After antibiotics became common, once-fatal infections became only minor inconveniences. But now it appears that bacteria, the target of antibiotics, are fighting back by developing resistance to the drugs that once killed them. In order to grasp how this has occurred, we need to understand a little more about both antibiotics and bacteria.
Antibiotic literally means against life. Antibiotics are natural substances, compounds made by living organisms, which either kill or inhibit the growth or production of bacteria. The antibiotics we take when we are ill are manufactured. They have been altered or synthesized in order to enhance their potency or increase the range of the species they affect. Some antibiotics, such as tetracycline, interfere with the production of new bacteria by binding to ribosomes and thereby preventing them from manufacturing proteins. Others, among them penicillin, obstruct the synthesis of cell walls. Whatever their mode of operation, antibiotics hinder the proliferation of bacteria and allow the human immune system to overcome any remaining organisms.
Bacteria are complex one-celled organisms. Contrary to popular belief, most bacteria are necessary and beneficial. Beneficial bacteria aid digestion, decompose dead organisms, and often protect us from an invasion of harmful bacteria.
Genomic or chromosomal DNA in bacteria is in the form of a continuous strand. This circular DNA is located in a nucleoid.1 A plasmid, another form of DNA, is an extra-chromosomal self-replicating structure found in bacteria cells. Plasmids, which carry genes for a variety of functions not essential for cell growth and normal survival, can be thought of as mini-chromosomes.
Compared with genomic DNA, which may contain 4 million base pairs, plasmids are small -they contain only 1,000 to 25,000 base pairs. A bacterial cell may contain one plasmid, many copies of the same plasmid, several different kinds of plasmids, or no plasmids. It is generally believed that DNA in plasmids helps bacterial cells to overcome the various stresses in their environment. One such survival mechanism is a gene or several genes for antibiotic resistance. Plasmids also may carry genes for virulence. For example, the severe food-borne disease caused by a strain of E. coli is a plasmid-based illness.
As bacteria usually reproduce through binary fission, or splitting to form two identical daughter cells, there is no recombination of DNA. However, many bacteria do exchange and then recombine genetic information through transformation, transduction, or conjugation. All three techniques have been exploited by specialists involved in the genetic engineering revolution.
When a bacterium (donor) dies, the cell ruptures (lyses) and thereby sets the cellular material free in the environment. Fragments of this naked DNA are then absorbed by recipient (host) bacteria, which incorporate and recombine it with their own. This process, known as transformation, has been exploited to produce such transgenic organisms as cows or plants that contain functional human genes.
The second method of recombination is transduction, or the exchange of genetic material by a viral carrier. Viruses that invade bacteria are called bacteriophages, or just phages by most scientists. When a phage infects a bacterium, it injects its own DNA, which then takes over the host’s metabolism and turns it into a small factory capable of assembling more phages. After it has produced a sufficient number of viruses, the cell lyses and the new phages are released and begin to infect more bacteria. If some of the host DNA is incorporated into a phage during the assembly process, an extremely rare occurrence, the defective phage still can bind to and inject its DNA into a host cell. However, it does not carry the virus’ genetic material and so cannot infect the cell. Thus it is no more than a mode of transport for DNA from one bacterium into another. As in transformation, the new DNA can be recombined with that of the host.
In the 1950s, scientists observed a third form of recombination: conjugation. This form of exchange features bacteria that are connected to each other through a tube or bridge. Donor cells carry fertility (or sex) plasmids, which allow the cell to synthesize long, thin hollow tubes called pili. The “sticky” pili bond to the cell walls of the recipient cell, and the two cells become united. A special enzyme then cuts a strand of the donor DNA, which is then transferred. Sometimes an entire chromosome is transferred and then recombined in the recipient cell. Bacteria also exchange plasmids through the conjugation bridge. This exchange is rapid and efficient. Not only do exchanges take place among bacteria of the same species, but they also cross species lines and even occur between bacteria and eukaryotic (plant and animal) cells.
Resistant genes work in several ways. Certain genes prevent destruction by producing enzymes that either degrade antibiotics or alter them chemically so that they become ineffective. Another gene helps the bacteria replace the receptor site for the antibiotic, thereby preventing it from binding to the bacteria. And yet a third gene can be used to manufacture a pump that removes the antibiotic from the cell.
When antibiotics are taken, the bacterial cells that are susceptible to the drug die. But some cells may survive. Those cells then reproduce and pass on that resistance to the daughter cells. This often happens when too little of a drug is used or if it is not taken over a long-enough period. If patients do not take enough of their prescribed medication or stop taking it after a few days, they are promoting resistance. Another problem is that non-life-threatening illnesses, such as acne and chronic ear infections, often are treated with low doses of antibiotics over a long period of time. This practice also aids the development of resistant genes.
Many patients view antibiotics as a quick cure, and unfortunately doctors succumb to demands to prescribe them even if they are not necessary. Although antibiotics do not kill viruses, they are prescribed for patients who do not want to be told just to go home, rest, and drink plenty of fluid. Unless a culture is done to identify the infection, a doctor can only guess which anti-biotic to use. Increasingly stronger or broader-spectrum antibiotics are employed in cases involving unidentified infections, which can be analogous to killing a fly with a machine gun. Most minor illnesses will succumb to the body’s immune system. Furthermore, we need to remember that the symptoms being treated are the body’s reaction to invasions by pathogens.
In many developing countries, antibiotics are available without prescription and are taken inappropriately. Some pharmaceutical companies offer doctors bonuses and gifts for every prescription they write, and so antibiotics are overprescribed.
The United States Food and Drug Administration (USFDA) reports that over 40 percent of all antibiotics produced in the U.S. are given to animals. Low doses of antibiotics are routinely fed over the lifetime of meat-producing animals to promote growth and improve feed conversion. This practice creates a perfect environment for the development of resistant genes. One example, which already has produced dire consequences, is the emergence of a strain of salmonella that is resistant to several antibiotics commonly used to treat it.
Antibiotics are routinely sprayed on crops to treat and prevent disease. Although bacteria that invade plants are not harmful to people, many are related to those which cause such food-borne illnesses as E. coli, salmonella, and shigella.2 If plant bacteria develop resistance, they could pass it on to bacteria that infect humans. There also appears to be evidence that we acquire resistant bacteria from our food. One researcher, Denis E. Corpet of the National Institute of Agricultural Research, has discovered that the amount of resistant bacteria humans obtain from food is quite significant. When his volunteers went on a diet of bacteria-free food, the quantity of resistant bacteria in their feces diminished by 1,000-fold.
Merri Moken, a student in Morristown, NJ, found that bacteria quickly developed resistance to common household disinfectants. The consequences of the proliferation of new anti-bacterial soaps, steering wheels, sponges, toys, and toothbrushes that we have seen in the past few years could be quite serious if it is causing an increase in resistance.
The first step in combating resistance should be to reduce the number of antibiotics used for treating illness. When possible, doctors should identify the pathogen before prescribing antibiotics. Patients should complete the full course of antibiotic treatment by taking all of their medication instead of saving some for later. They also should not demand these drugs for colds or minor infections. Second, developing countries should enact legislation to control sales of antibiotics without prescriptions.
Another important step is a drastic reduction in the use of antibiotics in agriculture. Routine feeding of antibiotics to meat-producing animals needs to be prohibited. Some European countries, Sweden for example, have banned the use of these drugs for growth promotion. Consumers should demand antibiotic-free meat. The practice of spraying fruit and vegetable crops, even though they are not infected, also needs to stop, and consumers should be encouraged to wash all produce thoroughly in order to remove bacteria and antibiotic residues.
Consumers need to consider the consequences of overusing disinfectants and anti-bacterial products. Generally, washing your hands with ordinary soap is all that is necessary if we have been exposed bacteria in public places. Perhaps more education on the necessity of bacteria is another solution.
Finally, new antibiotic drugs need to be developed so that we will continue to have a last line of defense against resistance genes. Other research designed to improve our understanding of all of the mechanisms of resistance could perhaps result in a new family of drugs. In our ever-shrinking world, it has become essential for us to consider the significance of our impact on other organisms, including bacteria. Bacteria were created with a purpose and are indispensable. So let’s stop waging war on all of them. We need the susceptible bacteria as our allies against those which are resistant