What’s that smell?
Do you remember the last time you were caught outside in the rain? Do you remember what it smelled like? If you were walking through a field or the local park, you might remember a deep, earthy smell, usually associated with wet soil. Have you ever considered where this smell comes from?
The smell of wet soil, known as “petrichor,” comes from a compound called geosmin that is made by a very special type of bacteria: Streptomyces. Streptomyces are one of the hundreds of bacteria that make up the dynamic microbial communities found in soil. And while it’s true that Streptomyces smells great—opening an incubator full of geosmin-producing Streptomyces smells like a spring rainstorm—they’re not just another pretty face in the microbiology world. Streptomyces, and their relatives, play a crucial role in human health and society. Not bad for some smelly soil bacteria.
Why are Streptomyces special?
What makes Streptomyces so great? In short, Streptomyces are a pharmaceutical powerhouse. Over two-thirds of the natural-product antibiotics that we use to treat infections in humans and animals are chemical compounds that are made by different types of Streptomyces bacteria. These bacteria also make many compounds that are used in chemotherapy, to treat fungal infections, or as herbicides.
How are Streptomyces able to make so many compounds? Each Streptomyces species (of which there are hundreds) contains several sets of genes in their DNA that are called “biosynthetic gene clusters.” These clusters contain the genetic information necessary for that Streptomyces species to make a particular compound, usually referred to as a specialized metabolite. Each Streptomyces species might have ten to forty biosynthetic gene clusters in their genome, with different clusters containing the information for different specialized metabolites. For example, Streptomyces venezuelae contains a biosynthetic gene cluster that, when activated, causes the bacteria to produce chloramphenicol. Chloramphenicol is an antibiotic that can be used to treat serious bacterial infections in humans and is included on the World Health Organization’s List of Essential Medicines.
Making these specialized metabolites takes a lot of energy and resources for Streptomyces, so the bacteria don’t keep these genes active all the time. Instead, they turn them on and off depending on several factors. Different biosynthetic gene clusters are activated by different triggers, but one important factor is the stage of growth. As a Streptomyces colony grows, it progresses through several distinct growth stages, eventually forming spores that are dispersed into the environment (Figures 1 and 2). Most Streptomyces species only activate some of their biosynthetic gene clusters once they reach these later stages of development.
There are also many environmental signals to consider. Microbial soil communities are complex ecosystems that researchers don’t yet fully understand. There are several environmental cues, like changing pH, temperature, available nutrients, and chemical signals from other microbes that can trigger or repress biosynthetic gene clusters. One important area of Streptomyces research right now includes trying to understand how biosynthetic gene cluster activation is controlled. The idea behind this research is that that if we better understand how these clusters are regulated, and what signals might trigger them, then perhaps we can use this knowledge to turn on new biosynthetic gene clusters and utilize their metabolites as novel medicinal compounds.
An Evolutionary Arms Race: The Rise of Antimicrobial Resistance
Prior to the mass availability of antimicrobial drugs*, something as minor as a scratch could quickly become lethal if infected, and infections were as big a killer as any weapon. The discovery of penicillin in 1928 and its release to public use in the 1940s marked the start of a new era in healthcare. The decades that followed saw the arrival of a plethora of new antimicrobials, most of which were developed from specialized metabolites produced by Streptomyces and other soil-dwelling bacteria or fungi. Antimicrobials (alongside other dramatic improvements in public health measures like vaccination and handwashing) significantly decreased the risk of fatality associated with events like traumatic injuries, childbirth, or food and water borne illnesses. They also made elective surgery more feasible by minimizing the otherwise significant infection risk associated with these procedures. However, we are increasingly at risk of losing all the health benefits we’ve gained due to the rise of antimicrobial resistance.
*A note on terminology: “antimicrobial” drugs are drugs that either inhibit or kill any type of microbe, be it bacteria, fungi, virus, or parasite. “Antibiotics,” although a commonly used catch-all term, are really a subclass of antimicrobial that specifically treat bacterial infections. We’re facing a resistance crisis with all forms of antimicrobials, although antibiotics are the most well-known component of this issue.
All living things evolve in response to their environment, and microbes are no exception. Over the years microbes have evolved many ways to survive exposure to toxic antimicrobial compounds. For example, some bacteria have special cellular machines that can pump toxins out of their cells, or even have enzymes that can directly inactivate antibiotics. Microbes with these types of resistance mechanisms are not new. But as we have increased our own commercial and personal antimicrobial usage in the past hundred years, these resistant microbes have also increased in prevalence because they have the traits to survive the higher antimicrobial exposure to which we are subjecting them. “Super-bugs” like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are just a few types of antimicrobial resistant bacteria that are now causing problems in hospitals and communities around the world.
Fighting Antimicrobial Resistance: Solutions in the Soil
What can we do to combat antimicrobial resistance? Antimicrobial resistance is a complicated problem with many different factors, so we are going to need collaborative and multifaceted solutions. Among other things, we need to better manage our antimicrobial usage, improve public health measures, and develop new drugs and techniques for treating infections.
One direction for discovering new antimicrobials is to study the diverse microbial communities that are present in the soil. Because there are many different soil environments, and thus many different microbial communities, sampling microbes from lots of different soils is one strategy that has been adopted in the search for novel compounds.
To do this, researchers collect soil samples from around the world and then study microbes from those samples. They use a variety of tests to look for microbes that can produce specialized metabolites and then test these metabolites for antimicrobial properties. The Wright Actinomycete Collection (WAC)—part of the work from the lab of Dr. Gerry Wright at McMaster University—contains thousands of different types of bacteria collected from several different environments, all of which are being used in research to combat antimicrobial resistance.
Soil sampling can even be crowd-sourced. The Tiny Earth project, created by Dr. Jo Handelsman at the University of Wisconsin, works with students around the world to sample their local soils for potential antimicrobial producing organisms. All of this work is leading us towards a better understanding of the microbial communities within soil, and hopefully towards new compounds that we can use to treat resistant microbial infections. Combined with research in phage therapy, chemical synthetics, and public health, soil microbe metabolites show promise in helping us combat resistance. So the next time you get caught in the rain, don’t let it dampen your day! Instead, take in the sights and smells and remember that there are some truly scent-sational microbial communities doing amazing things right below your feet, and helping you stay healthy in the process.
Article by Emma Mulholland
Emma Mulholland recently obtained her Master’s degree in biology, studying gene regulation in Streptomyces venezuelae at McMaster University. Her work focused on understanding how these fascinating bacteria turn their genes on and off throughout their lifecycle, and how they respond to changes in their environment.