Trojan horse predators

A while ago, Angry by Choice wrote a post about a fungi that kills its nematode prey by making little lasso ropes to catch the worm in. At the time, I thought there must be some exciting way that bacteria could cause wormy destruction, but it wasn't I read a paper from Lucas (reference below) that I actually found one.

It's not as visually exciting as the little fungi nooses, but it's just as chemically exciting. As bacteria are not capable of forming phyiscal structures to capture a worm, they make chemical ones, specifically volatile chemicals which diffuse easily and can be sensed by the worm.

In layman terms they smell good. They smell like food.

This is officially the best MS Paint picture I've ever done

Nematodes don't have a huge number of well programmed behaviours in their little nematode brains, but "move towards food" aka "positive olfactory chemotaxis" is one of the most robust and common behaviors. And the bacteria take full advantage of this. They secrete chemicals that are based on modified quorum sensing molecules (usually used for bacterial communication), which cause the worms to not only arrive where the bacteria are waiting, but also to happily gobble them up, after all they do smell like food.

Once eaten, the bacteria end up in the worms digestive tract, where they start to secrete enzymes - two digestive proteases called Bace16 and Bae16. Although previous work had assumed that these two proteases worked on the outside of the worms cuticle the paper used flourescent labeling studies to show that both Bace16 and Bae16 had their effects once inside the worm. Bace16 (labelled in red) and Bae16 (labelled in green) were both injected into an unsuspecting worm, which was then visualised every hour:

Images taken after 2hs, 5hrs, 8hrs and 24hrs - from the reference.

It's a little hard to see in the small picture above, but it is clear that the worm is getting ill, breaking apart, and finally just decomposing due to the action of the two proteases. The bacteria is not using the proteases to break into the worm, but to break out of it, digesting the worm in the process. This was further proved by making bacterial strains with the genes for Bace16 and Bae16 knocked out. Infection with the knockout strains led to far less virulent bacteria, and worms that survived for far longer.

It's an interesting new type of predation - a kind of Trojan Horse predator. Rather than chasing its prey, or directly infecting it, the bacteria gets itself eaten and then destroys the worm from the inside out. The paper suggests that as well as being interesting, this knowledge could help lead to more efficient biocontrol strategies for the elimination of nematode worms, now we know the active series of events involved in nematode predation by bacteria.

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Niu Q, Huang X, Zhang L, Xu J, Yang D, Wei K, Niu X, An Z, Bennett JW, Zou C, Yang J, & Zhang KQ (2010). A Trojan horse mechanism of bacterial pathogenesis against nematodes. Proceedings of the National Academy of Sciences of the United States of America PMID: 20733068
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Strategies of Intracellular Parasites

Intracellular parasites have a difficult life. On the one hand, they need to utilise the resources of the host cell, which will ultimately cause it damage, however on the other they must necessarily keep the host cell alive so that they can live off it. This is particularly difficult when your host cell is a eukaryote cell in a multicellular organism, because multicellular organisms can't afford to have one cell behaving oddly. If the cell starts to notice any differences in its behaviour, it promptly commits suicide, meaning that in order for the parasite to survive it has to find ways of preventing the cell from killing itself when it notices things going wrong.

Chlamydia is a particularly well studied human intracellular bacteria, and is best known for being sexually transmitted and featuring in posters on student welfare notice boards in probably every university in the UK:

If it's worth talking about, it's worth blogging about!

The reason Chlamydia is so worth talking about is two-fold, firstly because it's a bacterium rather than a virus and can therefore be (relatively) easily treated with antibiotics. Secondly, because you don't always know you have it and therefore it's worth getting tested even if you don't appear to have any symptoms. The bacteria can live perfectly happily within your cells replicating away without the body noticing, and if left untreated can lead to quite serious problems, such as blindness, pelvic inflammation or sterility.

In order to remain replicating inside the cells unnoticed for so long, Chlamydia have to prevent the cells from either destroying them or committing suicide before they manage to replicate. One of the ways they can do this is by degrading the cell proteins involved in cell signalling pathways. An example is the serine protease (i.e an enzyme that breaks down proteins) CPAF which is secreted by the infective chlamydia particles and (among other things) breaks down the protein HIF-1 which is used to trigger the cell suicide response to low oxygen levels. They can also break down proteins which would potentially be involved in the immune responses to the damaged cell, such as NF-KB, which helps activate the innate immune system inflammatory response.

Quite how the chlamydia causes the host cell protein degradation is still a little unclear. They may use the common viral strategy of modifying proteins to make them more susceptible to being picked up by the cellular degradation machinery (although there is no biochemical evidence for this as yet) or alternatively it might activate protein degradation pathways that are usually silenced in uninfected cells. Analysis of the chlamydia genome shows several predicted proteases, so it may be possible that rather than using host proteases the bacteria is degrading specific proteins with its own protease enzymes. The bacterial protease CPAF (mentioned above) has been crystallised and the crystal structure shows the potential for several different substrates (i.e it could potentially degrade many different proteins) so it might play in important part in this process.

The use of degradation proteins also creates a potential target for therapeutics. If that sentence sounds familiar it's because I've written it several times before and will probably write it several times in the future. "New targets for therapeutics" is pretty much THE standard excuse for studying anything related to bacteria. From a more selfish and less funding-motivated standpoint, it also provides exciting new information about how bacterial and eukaryotic cells interact, and how parasites that live inside cells can control host signalling pathways to their own advantage.

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Zhong G (2009). Killing me softly: chlamydial use of proteolysis for evading host defenses. Trends in microbiology, 17 (10), 467-74 PMID: 19765998

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