The discovery of antibiotics was one of the greatest medical breakthroughs in human history, but it was quickly followed by the rise of antibiotic-resistant pathogens. Now, nearly 80 years after the introduction of antibiotic drugs, multi-drug-resistant bacteria plague hospitals, and once-tamed diseases like tuberculosis are making a comeback. But where exactly do human pathogens acquire the genes that make them resistant to antibiotics? New research shows that the answer could be ... everywhere.
The widespread problem of antibiotic-resistant pathogens is commonly blamed on the fact that we use antibiotics too aggressively: physicians overprescribe them and farmers routinely keep their livestock on them. This is a problem because, as the story goes, by saturating ourselves and our environment with antibiotics we've created conditions ripe for the evolution of antibiotic-resistant bacteria. Since bacterial populations tend to range in the trillions, it's not surprising that there will be a few individuals bearing a lucky mutation that enables them to survive and reproduce in the presence of antibiotics. To avoid this evolutionary scenario, we need to limit our use of antibiotics to situations when they are absolutely necessary.
We're swimming in a vast reservoir of antibiotic resistance genes.
As it turns out, this evolutionary story is too simple. Bacteria have a fast track to antibiotic resistance because they have the ability to swap genes. Bacteria are generous with their genes, sharing them even with members of other bacterial species. The possibility of bacteria trading antibiotic resistance genes was first suggested in the 1950s, and in a groundbreaking paper in 1973, two scientists showed that common soil bacteria and pathogenic Streptomyces share the same specific type of resistance to the drug gentamicin. However, for decades there was not much evidence that gene swapping with environmental bacteria played a major role in the emergence of resistant pathogens.
That evidence is now coming in, and it shows that we're swimming in a vast reservoir of antibiotic resistance genes. Using a new method called "functional metagenomics," scientists are searching for resistance genes by collecting bacterial DNA from the environment and testing its function in harmless lab bacteria. Researchers have collected DNA from a wide range of environments, including the human gut, city soil, remote Alaskan wilderness, processed sewage, and even 30,000 year old Beringian permafrost. Antibiotic resistance genes were found in each of these environments.
Human pathogens are swapping resistance genes with these environmental reservoirs. Last year, my Washington University colleagues working in the laboratory of Gautam Dantas reported that they had found seven resistance genes in soil bacteria that were completely identical to genes in pathogens from human clinical samples. This finding is the strongest evidence to date that pathogenic bacteria are exchanging resistance genes with bacteria in the environment. As scientists scour the newly accessible genetic landscape of our bacterial environment, they will uncover many more examples.
Perhaps more disturbing than the swapping of antibiotic resistance genes is what has not yet been shared. Dantas and other scientists have discovered dozens of exotic new types of antibiotic resistance genes that have not yet been seen in human disease, but which are out there lying in wait. Many of these genes appear to have normal functions that do not involve defeating antibiotics, but they can be recruited for antibiotic resistance when the host bacteria is exposed to a drug. Because these genes have functions unrelated to antibiotics, they can hang around in the bacterial population even without the evolutionary pressure of antibiotic overuse.
These recent studies show that genetic reservoirs of antibiotic resistance are everywhere, and that the capacity to defeat antibiotics existed long before humans began using antibiotic drugs. While there is no question that our overly aggressive use of antibiotics has contributed to the rapid spread of drug-resistant pathogens, resistance was going to show up sooner or later regardless of how judiciously we used antibiotics. Cutting down on our antibiotic use at this point is important, but it is a delaying action; we need a new strategy. In a recent review of the new functional metagenomic studies, Dantas and his colleagues point to a few possibilities: antibacterial vaccines, and viruses that prey on bacteria. Strategies like these are largely in their infancy, but they will be crucial in our ongoing battle with pathogens.