Life at zero growth rate - SGM series

This is the third post in my latest SGM series.

One of the first topics that I learnt in Biology was that there are two types of things; living things, and dead things. Living things are given a whole host of distinguishing characteristics (growth, reproduction and, my favourite, irritability) where as dead things are defined as everything else. Biology was usually defined as the study of living things.

As I grew older, I found that there were many complications to this neat little classification. Viruses - which are neither fully living, nor properly dead. A whole organism can be dead, despite the fact that many of its cells are still alive (how alive is a freshly killed animal? Or the flowers in a vase?). And of course what is for me the most intriguing case, that of dormant bacteria.

Dormancy is an odd state to be in. A dormant organism shows none of the signs of being alive. It does not eat, grow or divide (although some very basic metabolic processes may still continue). It shows no response to any outside stimulus, and can often be placed in conditions that would

lead the living organism to perish, such as extremes of temperature and pressure. Yet somehow just one simple stimulus can cause this previously dead looking organism to spring magically back into life.

Bacteria are not the only things that can go dormant. Some

animals can as well, the most famous example being tardigrades -the thing shown on the right that looks a bit like a plushie made by Tim Burton (image from wikimedia commons). Yeast are well-known for forming dormant spores, and it can be argued that a seed is technically a dormant plant, just waiting for water to be added to bring it back to life.

One of the most medically important dormant bacteria is Mycobacterium tuberculosis which infects humans and leads to TB. One of the reasons for its pathogenicity is that they can go dormant, both outside the body (which makes them hard to shift from a hospital) and inside the body, after the primary infection (which makes them even harder to shift from inside a human body).

Although the latent cells can remain within the body for many years, sometimes never coming back from dormancy at all, ideally there should be some signal to bring them back to life. These signals are known as "resuscitation-promoting factors" or RFPs. These RFPs are required for virulence, and to bring the bacteria back from dormancy, but are not necessary for the growth and proliferation of cultures in the lab.

Within human tissues, and throughout the cycle of the disease, you can track these RFPs to try and get an insight into what the bacteria is up too, and when it may move from latent periods to periods of active growth. As well as being useful for tracking the course of infection, this might also have therapeutic implications. If you can convince the bacteria not to come out of dormancy then you have an infection state that might not be completely curable but is at least controllable.

How organisms survive in a state of dormancy, and indeed how they ever come out of it, is a subject I find really fascinating. I'm unlikely to ever get to do much research on it (because as fascinating as it might be screwing around with my little bugs till they do what I want is endlessly more fun) but I'll probably have a good few more posts writing about it and exploring how it works.

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Kana BD, Gordhan BG, Downing KJ, Sung N, Vostroktunova G, Machowski EE, Tsenova L, Young M, Kaprelyants A, Kaplan G, & Mizrahi V (2008). The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Molecular microbiology, 67 (3), 672-84 PMID: 18186793

Davies AP, Dhillon AP, Young M, Henderson B, McHugh TD, & Gillespie SH (2008). Resuscitation-promoting factors are expressed in Mycobacterium tuberculosis-infected human tissue. Tuberculosis (Edinburgh, Scotland), 88 (5), 462-8 PMID: 18440866