E. coli is boring, admit it. At least in comparison with Myxococcus xanthus: a self-organized, predatory saprotrophic single-species biofilm called a swarm according to the Wikipedia. Now that sounds exciting! I wish one day somebody would call me "a self-organized, predatory biofilm called a swarm"! That would make a lovely email signature: "Vasili Hauryliuk, PhD, self-organized, predatory biofilm called a swarm". Hell yes.
Harris BZ, Kaiser D, & Singer M (1998). The guanosine nucleotide (p)ppGpp initiates development and A-factor production in Myxococcus xanthus. Genes & Development, 12 (7), 1022-35 PMID: 9531539
But I digress. Stringent response (or, to be more specific, RelA-mediated production of alarmone molecule ppGpp) regulates loads of things in bacterial physiology: it turns on bacterial survival mode and shuts down production of ribosomes, it induces virulence (cornered bacteria are deadly) and makes bugs more resistant to antibiotics. Now let us just imagine for a moment what stringent response can do to a "a self-organized, predatory biofilm called a swarm"! Exactly that was investigated in recent paper by Konovalova and colleagues (Konovalova et al. Mol Microbiology 2012).
Unlike boring E. coli, Myxococcus xanthus has a life cycle (Fig. 1). It can swarm happily gobbling up other bacteria, or, if food supply is low, it can form a fruiting body (a life-stile similar to that of slime molds who are not bacteria but eucaryotes).
Fig. 1. Life cycle of a self-organized, predatory biofilm called a swarm (AKA Myxococcus xanthus).
Formation of the fruiting bodies depends on the functionality of the stringent response system (Harris et al. Gens Dev. 1998). How Konovalova and colleagues fill in the molecular details presenting an example of post-translational activation of secretion by regulated proteolysis. Here is how it works.
Formation of the fruiting bodies depends on the cell-to-cell signaling, and this process, obviously, happens outside of the cell. It involves proteolysis of several extracellular target proteins by a subtilisin-like protease PopC, which needs to be exported outside of the cell in order to do its job. So now it turns out that RelA, working together with PopD protein, regulates PopC export, which is activated during starvation (and, therefore, production of ppGpp). The PopD:PolC complex formation is not affected by ppGpp, suggesting that regulation of export by RelA is using some indirect mechanism. And indeed, PopD turned out to be degraded during starvation in a FtsH-dependent manner, releasing PopC - a story somewhat similar to regulation of toxin:antitoxin pairs via antitoxin degradation by Lon protease during nutritional stress.
All this brings us to the question of importance of the regulated proteolysis during the stringent response. One known example of ppGpp-mediated control via protein degradation is degradation of ribosomal proteins by Lon protease induced by accumulation of polyphosphate. Unfortunately, usually stringent response on the whole-cell level is studied on the mRNA level, by, say, microarrays. It would be most educational to compare the changes on the mRNA level with changes on the proteome level and to pick up the protein degradation-mediated regulation pathways.
References:
Unlike boring E. coli, Myxococcus xanthus has a life cycle (Fig. 1). It can swarm happily gobbling up other bacteria, or, if food supply is low, it can form a fruiting body (a life-stile similar to that of slime molds who are not bacteria but eucaryotes).
Fig. 1. Life cycle of a self-organized, predatory biofilm called a swarm (AKA Myxococcus xanthus).
Formation of the fruiting bodies depends on the functionality of the stringent response system (Harris et al. Gens Dev. 1998). How Konovalova and colleagues fill in the molecular details presenting an example of post-translational activation of secretion by regulated proteolysis. Here is how it works.
Formation of the fruiting bodies depends on the cell-to-cell signaling, and this process, obviously, happens outside of the cell. It involves proteolysis of several extracellular target proteins by a subtilisin-like protease PopC, which needs to be exported outside of the cell in order to do its job. So now it turns out that RelA, working together with PopD protein, regulates PopC export, which is activated during starvation (and, therefore, production of ppGpp). The PopD:PolC complex formation is not affected by ppGpp, suggesting that regulation of export by RelA is using some indirect mechanism. And indeed, PopD turned out to be degraded during starvation in a FtsH-dependent manner, releasing PopC - a story somewhat similar to regulation of toxin:antitoxin pairs via antitoxin degradation by Lon protease during nutritional stress.
All this brings us to the question of importance of the regulated proteolysis during the stringent response. One known example of ppGpp-mediated control via protein degradation is degradation of ribosomal proteins by Lon protease induced by accumulation of polyphosphate. Unfortunately, usually stringent response on the whole-cell level is studied on the mRNA level, by, say, microarrays. It would be most educational to compare the changes on the mRNA level with changes on the proteome level and to pick up the protein degradation-mediated regulation pathways.
References:
Konovalova A, Löbach S, & Søgaard-Andersen L (2012). A RelA-dependent two-tiered regulated proteolysis cascade controls synthesis of a contact-dependent intercellular signal in Myxococcus xanthus. Molecular Microbiology PMID: 22404381
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