“If you can’t grow them, you can’t study them.”
This was the reality for early microbiologists. Traditional microbiology relies on culturing: a process that involves isolating microbes, recreating their ideal environmental conditions in petri dishes or flasks, and feeding them specific nutrients to coax them into growing. This helps us understand their biology, behavior, and role in nature, and is essential for identifying pathogens, diagnosing infections, and developing treatments.
But what if I told you that most microbes refuse to cooperate? Maybe they’re just shy? In fact, for every microbe we’ve successfully cultured, hundreds – if not thousands, remain unculturable. This raises a key question: do we really need to grow them all to study them?
Bacteria usually don’t like to grow in unfamiliar places. Although some will happily grow and are thankful for whatever you feed them, others are very picky, demanding exact nutrients. Some are painfully slow growing, while others depend on specific growth factors or metabolites produced by their neighbors – conditions we often disrupt by isolating them. And then there are those that … just don’t want to grow. Hey, I totally get it – if I were a microbe, I’d probably prefer the ocean over a lab flask too.
Now imagine trying to grow a bacterium from the deep sea. How would we recreate these conditions in the lab? You’d need crushing pressures, toxic chemicals, constant darkness, and maybe even a symbiotic host organism that the bacterium has co-evolved with for millions of years. No big deal, right? It’s like attempting to recreate a tropical island in your backyard. In other words, recreating this environment is extremely challenging. Despite these hurdles, researchers over the years have developed special culturing methods to grow a small fraction of deep-sea microbes. If we still can’t grow most microbes, then how do we study them?
Enter high-throughput DNA sequencing and computational tools. While culturing remains essential for studying microbial physiology, culture-independent methods, like metagenomics, sequence all the DNA directly from an environmental sample; be it soil, seawater, the human gut, or even a hospital sink. We then use powerful computers to analyze this DNA data to piece together microbial genes and genomes, which gives us information to answer two key questions, amongst many others:
1) Who’s there?
2) What are they doing?
The actual community of bacteria, archaea, fungi, and viruses in a specific habitat (like your gut, or the ocean), is called the microbiome. This term is often used in the context of host-associated microbial communities, such as the human microbiome. Metagenomics has revealed how imbalances in the human microbiome, or dysbiosis, have been linked to diseases like diabetes, obesity, and even neurodegenerative disorders.
For decades, microbiology was limited to the few microbes willing to grow under lab conditions. But metagenomics gives a voice to the uncultured majority: uncovering microbes that play critical roles in health, ecology, and evolution. This approach has revealed new species, unknown genes with industrial applications, and unique metabolic capabilities we didn’t even know existed. And for researchers like me, it’s a key tool for studying rare marine microbes that thrive in Earth’s oceans.
At the LaRoche Lab, we try to grow hard-to-culture microbes, like the T. haligoni bacterium my colleague Sonja Rose successfully grew from Halifax’s own Bedford Basin. At the Beiko Lab, we use and develop computational tools to study how these microbes interact and share genes. Together, these approaches give us the best chance to understand microbial life in all its complexity.
Photo by National Cancer Institute on Unsplash
