by Mechas
Most of us have at some point used antibiotics. These "miracle drugs" stop infectious bacteria from growing out of control, essentially curing us from what could be fatal infections. But antibiotics are also marvelous for other reasons. As natural products, they are a constant source of novel scientific insight. As drugs, they have become the very agents of a new pandemic: antibiotic resistance.
Many people rarely reflect on the fact that these miracle drugs, which were not broadly available for medical treatment just a century ago, have effectively liberated us from the anguish of losing loved ones to bacterial infections. Sadly, though, we are slowly heading towards a not-too-distant future that might resemble the past. This is due to the increase in antibiotic resistance amid those very pathogens we need to control. But where does this resistance come from and why is it considered a threat?
Antibiotic resistance test: Bacteria are streaked on dishes with white disks impregnated with different antibiotics. Clear rings, such as those on the left, show that bacteria have not grown—indicating that these bacteria are not resistant. The bacteria on the right are fully resistant to all but two of the seven antibiotics tested. Source. Frontispiece: Colonies of Streptomyces roseosporus cells produce droplets containing antibiotics. Source (image credit Scott Chimileski and Roberto Kolter)
Many antibiotics used today are produced by microbes themselves, mostly by bacteria that belong to the phylum Actinobacteria. Which, by the way, also includes the well-known pathogen Mycobacterium tuberculosis. This phylum contains a group of drug-producing microbes, informally known as the actinomycetes, that are also studied for their wonderfully complex biology: from their developmental pathways that lead to spore formation, to their slow growth physiology and, of course, their production of specialized metabolites, some of which are potent antimicrobials that have been exploited in medicine. Why some bacteria produce these antimicrobial metabolites is not fully understood, but several clues are provided by their roles in nature. In some cases, they provide signaling cues, in others they defend an associated host against infections. In most cases, however, the roles and production of these specialized metabolites in the wild remain a mystery.
What is known is that antibiotic-producing microbes contain resistance genes that protect them against the toxic effects of these molecules. Many of these genes are suspiciously similar to those we find in resistant pathogens in hospitals. Which of course points towards a possible origin of antibiotic resistance genes. But why do these genes arise in clinical settings where treatment of patients frequently results in resistance to one or several antibiotics? The answer is also incomplete but is rooted in evolution.
For one, we have increased both the production of antibiotics and their release into the environment. In the environment, these drugs inflict pressure on microbes and select for those that carry resistance genes. These microbes then move to other locations, inadvertently spreading resistances across the globe. Secondly, some of these genes can move to other bacteria via horizontal gene transfer, effectively distributing these markers across microbes. In doing so, they add to the already existing reservoirs of antibiotic resistance genes in the environment, some intrinsic to the population and others selected by contaminating antibiotics. Genes conferring resistance to antibiotics, both intrinsic and acquired, are widespread in the environment, from contaminated sewage sites to pristine polar regions. We are therefore surrounded by many microbes that carry antibiotic resistance genes. If they ever encounter antibiotics, as occurs in hospitals, they are already armed with defenses that will allow them to flourish while other, sensitive bacteria, will perish.
Antibiotic resistance is real and concerning, but it is also the result of our unintentional experiment on microbial evolution. How to counteract the growing tide of resistance is another matter. It requires both individual actions and concerted global efforts to control production and use. Consolidating such global strategies can be slow, especially when compared to microbes who, after all, respond efficiently by doing what they do best: evolve to survive.
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