Two Component Systems

For free-living (especially free-moving) organisms, the ability to sense and respond to the outside environment is crucial for survival. Eukaryotes, such as animals and plants, often have highly complex network systems in place to monitor their surroundings and respond effectively, but bacteria have developed a remarkably simple system. It's called the 'Two component system' because it literally relies on just two components; a sensor and a responder. The sensor picks up the signal, communicates this to the responder, which then causes the effect.

The 'communication' of the message from the sensor to the responder, is carried out by transferring phosphate molecules. The signal interacting with the sensor, causes the sensor to autophosphorylate (phosphorylate itself) and then pass the phosphate molecule onto the responder, triggering the response, as shown in the diagram below:


Diagram drawn by me, using all the MS Paint skill I possess. (I've tried to keep the colours colour-blind friendly). Sensor in green, responder in blue, and the brown lines show the path of the phosphate. Blob on the left is the signal molecule that the system is sensing. 'H' and 'D' are amino acids Histadine and Aspartate respectively.

One of the most useful things about this system from a scientific point of view is that the phosphorylated regions are very well conserved across bacterial species. This makes them relatively easy to find, once you have the full genome of the organism, as shown by large-scale searches for two component systems in Bacillis subtilis and Streptomyces coelicolor (both references given below). In both organisms hidden Markov models were used to find the conserved protein sequences, and then sequence alignments carried out to group the sensors and responders into different groups. They also searched for transmembrane domains within the sensors to find whether (and how) they were attached to the surface of the bacterial cell. Unattached soluble sensors suggest a monitoring of the intracellular environment, whereas membrane bound sensors are more likely to provide information about external conditions.

As the function of many of the two component systems (particularly in Strep. coelicolor) is unknown, studies like this provide exciting new avenues of research to explore. One of the main commercial attractions to studying two component systems (ignoring the main attraction, which is simply to find out how the things work) is that they aren't present in animal cells, and therefore could potentially be a target for novel antibiotics. Particularly as many of them are vital for the survival of the bacteria, particularly opportunistic motile pathogens.

In fact, two component systems are very often the way the bacteria senses and responds to the antibiotics as well. Knocking out the vancomycin response system (VanRS) might not kill the bacteria, but combining it with vancomycin treatment would be deadly.

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Guest Posting

Work is sort of getting to be at the moment, now term has properly started there seems to be an awful lot of it happening, and everything is going slightly crazy. So if anyone would like to write guest posts (both blog-owners and non-blog-owners) they would be happily recieved. Leave some form of contact in the comment box (or write to me for those who know my email address) and I'll get back to you.

All I ask is that the posts be vaguelly about science. :)

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Fabret C, Feher VA, & Hoch JA (1999). Two-component signal transduction in Bacillus subtilis: how one organism sees its world. Journal of bacteriology, 181 (7), 1975-83 PMID: 10094672

Hutchings MI, Hoskisson PA, Chandra G, & Buttner MJ (2004). Sensing and responding to diverse extracellular signals? Analysis of the sensor kinases and response regulators of Streptomyces coelicolor A3(2). Microbiology (Reading, England), 150 (Pt 9), 2795-806 PMID: 15347739