Dear Microbes: Why won't you grow?!?!

The vast majority of the microbes on the planet are unculturable.

When you think of a microbiology lab, you might be faced with images of round petri dishes filled with gelatinous agar specked with small microbial colonies. Or you imagine microscopes and scientists lovingly peering down their binocular lenses to image indeterminately small single celled creatures.

The truth, I fear, is removed from these stock-photo worthy images.

As a geomicrobiologist concerned with the multitude of organisms that thrive in the deep subsurface, the truth is that you can’t grow the vast majority of these microbes. In fact, estimates say that 99% of all the microbes on earth can’t be grown at all in a laboratory. These organisms are known as unculturable due to their inability to be cultured following standard technique.

Why are these little bugs so resistant to our attempts at domestication?

Microbial communities tend to be complex and robust small-scale ecosystems filled with a complex variety of nutrients and many small cell-to-cell signaling molecules that can provide chemical encouragement for organisms to grow.

Also at fault is the fact that us humans tend to have human-shaped attention spans. In the subsurface, microbes may be content at dividing every hundred years, growing slowly in response to severely limited nutrients. Although that’s a fast rate in geological time, for graduate students and scientists eager to make discoveries, microbes that take thousands of years to grow are simply outside the observable range.

Enrichment cultures, where you enrich a particular growth media to support a robust consortia of microbes, is the standard environmental microbiology technique when it comes to a first attempt at coaxing microbes brought in from their natural habitat to grow.

These enrichment cultures have been instrumental in resuscitation of microbes from extreme environments including sea-floor hot spots, acid mine drainage systems, and deep within the subsurface.

Other advanced techniques include engineering environments exposed to different chemical gradients such as decreased oxygen concentration over a gelatinous agar media where microbes need a very specific oxygen level to catalyze redox sensitive reactions and/or lack the machinery to deal with high levels of oxygen in the atmosphere.

Even with these novel innovations, the vast majority of life can’t be cultivated. This is significant because without the ability to grow and closely study these organisms, trying to figure out their role in the subsurface, and what exactly they're doing, is hindered.

Instead, to study microbes, typical standard practice is to obtain a sample that you want to study: anything from core, drill cuttings, or water, extract the microbial DNA, and sequencing that DNA using a variety of techniques.

These so-called culture-independent techniques sidestep the difficulty in culturing microbes altogether, and instead return tens to hundreds of thousands of unique DNA sequences specific to the microbes originally present in the sample.  

Culture-independent techniques have ushered a golden age of microbial ecology and microbial genomics allowing visualization and insight into the depths of the biosphere never previously imagined. These advances continue to outpour in the scientific literature and empower biotech companies to innovate and improve the world around them.

There remains an ongoing gap between the ability to recognize and name the microbes scientists are finding in all niches of the planet and to understand holistically what function they are performing.  Given that up until about a decade ago the only way to study microbes was through these limited techniques of cultivation and direct observation, the advances being made in closing the observation-function gap are impressive and are working to bridge that chasm.