Monday, June 2, 2008

Dr Jekyll and Mr Hyde: Individuality in isogenic bacteria

Source: Pearl S, Gabay C, Kishony R, Oppenheim A, Balaban NQ (2008) Nongenetic individuality in the host–phage interaction. PLoS Biol 6(5): e120.

Individuality is a broad term; however, in genetic context it refers to phenotypic differences between individuals with identical genomes (e.g. identical twins). This paper studies bacteria vs phage interactions in isogenic backgrounds and the non-genetic choices that the entities in the community face individually. A clear example of such behavior is bacterial persistence in adverse environments; certain bacteria survive stresses (e.g. antibiotics) by shutting down the cellular processes and entering a dormant state.

Here, the authors have studied the influence of persistence as a choice in host-phage interactions in populations of bacteria. They have cloned a temperature sensitive cI (lambda repressor) in a lysogenic strain; in this strain, shifting to higher temperatures results in activation of lytic pathway and cell death. They compare the survival rate of wild-type and persister (hipA7 strain) strains upon switching to
a higher temperature (which leads to phage activation). They do this through measuring the activity of lytic genes (using GFP reporters cloned downstream of lytic promoters) and tracking cell-fate using live microscopy. The figure below, taken from the original paper, shows the higher survival rate of hipA7 strains.The authors also show that the phages cannot kill persister cells in their dormant state and they rely on the cell to switch back. To test this, they initially lyse all the hipA7 mutants that are active by an incubation in high temperature. Then they measure the exit from dormancy by locating the first occurrence of cell division. They simultaneously measure the activation of lytic pathway by a GFP reporter. Their results show a high correlation between the lytic pathway activity and exit from dormancy.

Now, what is the significance of these observations? These results clearly show the effect of persistence on host-phage interactions. In other words, a high persister strain (like hipA7) would overcome a low persister (e.g. wild-type) in an environment with frequent appearance of phages; whereas, in normal environments they should do worse given their lower growth rate due to a higher chance of dormancy. The au
thors actually test this model through competing wild-type and hipA7 strains with different frequency of phage inductions. This figure from the paper perfectly shows the hipA7 overcoming wild-type in high phage induction environments (red is hipA7 and blue is wild-type).


These observations imply that persistence in bacteria acts as a general immune response at the population level to overcome environmental and predator-prey stresses. In my opinion, this random entrance and exit from dormancy in response to predators and phages very much resembles the random strategies evolved in the behavior of higher organisms (from a game-theoric point of view). Simply put, bacterial communities are very well capable of complex behavioral concepts despite the evident lack of the nervous systems.

2 comments:

Unknown said...

This is an elegant example of how "fitness" can only be defined with respect to a specific environment. What looks like a slow-growing cell to us (and seemingly less fit) may in fact just be better adapted to a phage-filled environment. Cool :)

Hamed said...

What will happen if the environment switches between two conditions frequently? I mean, assume at first the environment is filled with phages, and then for some reason (drift? magic?) it becomes a peaceful land for happily ever after-living bacteria. Won't it be beneficial to both genotypes to try maintain the other one during each of these conditions, so as after a sudden change the before-troubled strain can come up and build the populatoin? I can think of simple means for this, such as a signaling in which phage-tolerant bacteria induce dormancy in rapid-growing ones and rapid-growing bacteria trigger a wake-up call in dormants. What do you think? Too crazy? I just think this mixed strategy would be more successful than each of them alone.