Written by Gautam Dantas, MD, professor in the Department of Laboratory & Genomic Medicine in the School of Medicine
Dr. Dantas and his team study the ecology, evolution and transmission dynamics of microbes and their antibiotic resistance genes across multiple habitats, towards building better predictive models of resistance selection and dissemination. Specifically he has recently focused on soil bacteria and solving the problems of antibiotic resistance.
Can you describe what you mean by “soil bacteria,” and some of the things you’ve discovered that make soil bacteria different from other bacteria?
There are a larger number of bacteria that live in soil environments, and I’d estimate that a gram of soil contains more diversity than our entire catalog of known bacteria. The diversity simply dwarfs everything else. For comparison, the average human gut as 100 to 200 different species and soil has many thousands of such species. Part of the reason for this is that bugs that live in the soil exist in much more variable conditions, with seasonal variation, geographic variation, and differences in nutrient availability, compared with those that live in and on mammals, in relatively stable conditions.
Drug-resistant bacteria represent a major public health threat. Can you outline some of the larger potential implications of your findings?
Almost all antibiotics we use today are natural products of soil-dwelling bacteria or their synthetic derivatives. So these bugs we find in the soil are a natural source of antibiotics. Soil bacteria are also the origins of antibiotics resistance—the original source must be in the soil.
In a paper published in Science in 2012, “The Shared Antibiotic Resistome of Soil Bacteria and Human Pathogens,” we explained that we were able to identify a particular set of drug-resistant bacteria that appear to be a ‘missing link’ between the clinic and soil, as this unique small group have exactly the same resistance genes as clinical pathogens. So ultimately, as these bugs become more and more dangerous, their neighbors that we’ve found in the soil can help lead the way to new antibiotic drugs.
We also published a paper in Nature in 2014, “Bacterial Phylogeny Structures Soil Resistomes Across Habitats,” showing that the majority of bacteria in the soil have resistance genes that do not appear poised for transmission to the clinic. Most Most soil resistance genes are not next to mobilization elements, as they were selected over millions to billions of years of evolution, compared to the relatively recent selection pressures on bugs we find in the clinic due to therapeutic antibiotic use. We hope to use this knowledge to identify ways to reduce gene sharing among infectious bacteria and other environments, and slow the spread of drug-resistant superbugs.
So if we put these two findings together, we can conclude that yes, there’s a lot of resistance in the soil bacteria, but most of it is not poised to jump into the clinic. However, this sub-group of multidrug resistant soil Proteobacteria has the potential to exacerbate resistance problems in the clinic.
What are the biggest challenges right now for infectious disease research?
There are a few major challenges. For one, antibiotic resistance is developing and spreading at such a rapid rate that we’re looking at a post-antibiotic era for many infections. The resistance is moving faster than we are, and we’re running out of drugs to treat these infections. A lot of research is focused on pathogenesis, which is still important, but it doesn’t matter if we figure out pathogenesis of infections if we can’t treat them.
Another issue I’ve encountered is the almost philosophical divide involved when researching bugs clinically versus in environmental analysis, or with taking a rigorous single-bug versus community approach. When you treat an infection, there’s lot of potential for collateral damage, which clinically isn’t typically taken into account. While we’re trying to model antibiotic resistance across ecologies, clinicians often ignore the interactions between pathogens and the rest of the microbial world. This divide between clinical and environmental microbiology is getting smaller because of increasing research interest in the human microbiome. But the challenge is to make sure that people who are our first line of defense, our physicians, are convinced that habitats for all bugs, both good and bad, are connected. A clinician may think of ecology as “fuzzy,” but we argue that the application of quantitative ecology principles will enable a more holistic approach to treating infectious diseases in the future.