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Francisella tularensis: another bacterium you should know more about November 1, 2006

Posted by Hegemony in Health, Science.
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Firstly, let me thank the agricultural biotech groups and newsletters that picked up my last post about GM crops. It’s nice you enjoyed it enough to distribute it, and for the record I have no qualms about it. This post will probably less divisive (read: popular) though.  I encourage people to comment, even argue with me if they want.  But seriously, I don’t speak German.  Certain individuals (you know who you are) obviously understand English well enough to be pissed off.  If you want to tell me off, do it in English.

Francisella tularensis is an intracellular pathogen that is a potential bioweapon. It causes the disease tularemia; there is no vaccine for Francisella. It infects and replicates in macrophages by a novel mechanism that sets it apart from other intracellular pathogens. It is capable of interfering with the fusion of the Francisella-containing phagosome (FCP) with the lysosome, thereby creating a niche for itself. This organism diverges from the accepted mechanisms of other intracellular organisms. There are four different subspecies of F. tularensis: tularensis, holarctica, mediasiatica and novicida. F. t. tularensis is the most common pathogen associated with humans.

Foreign particles are taken up by macrophages and degraded in low pH vacuoles called lysosomes. As with most intracellular pathogens Francisella tularensis must prevent the phagosome it is contained in from merging with the lysosomal vacuole. A phagosome is simply the vacuole that a bacterium is contained in after it is internalized. Different intracellular organisms have different methods of disrupting the fusion of the phagosome and lysosome. The more common method used by Legionella and Chlamydia involves exporting bacterial effectors to the cytosolic surface of the phagosome. This prevents it from merging with a lysosome and does not interfere with the biochemical processes of the cell. The second and less common method is for the pathogen to export effector molecules to the cytosol where they interfere with all endocytic vesicles.

F. tularensis has decidedly different properties and thus is unique. It is taken up by what appears to be a microtubule dependent mechanism. The macrophage’s compliment receptor may be involved with internalizing the bacterium. Interestingly, this same novel mechanism is seen even with heat or formalin killed F. tularensis. The phagosome is remodeled quickly after infection. The bacterium has an unknown mechanism for keeping the phagosome from becoming too acidic. By 3-4 hours after infection the membrane of the phagosome will be weakened and breaks down releasing bacteria into the cytosol at about the 8 hour mark. It is here that they will replicate. However, the same killed bacteria from above have been found to be degraded in lysosomes just as any other particle would be.

Despite how quickly F. tularesis replicates it cannot propagate in activated macrophages. Though, no known pathogen can. The mechanism for this varies from one pathogen to another. In this case it seems to be that the phagosome does fuse with a lysosomal vacuole. In addition to this the bacterium seems to be unable to affect the phagosome to break it down.

Recently new details of the pathogenicity have been discovered. A pathogenicity island (FPI) has been identified in several subtypes of Francisella. Many of the genes in the FPI are integral to the intracellular nature of F. tularensis. It seems likely that these gene products are needed for escape from the phagosome. This would explain why killed bacteria are degraded but can still be internalized normally.

This is a very interesting bacterium with many unknowns. With such a pathogenic organism it is important threat we unravel these mysteries as quickly as possible. The effects of infection can be truly horrible so we must not allow ignorance to be our downfall.

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