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21 Oct 2019

What do bacterial pathogens eat? - On the importance of basic research

Doherty Institute PhD student Miku Kuba wrote this blog entry following her recent success in getting her work published in the Biochemical Journal.

Miku writes regularly about her life as a PhD student on her blog A Bug's Life.

When I tell people I work on bacteria, the general conversation ends up flowing like this.

‘What bacteria do you work on? What illness does it cause?’

‘Does that mean you’re going to find a cure?’

‘Maybe you’ll win a Nobel Prize?’ *cue awkward laughter*

Many infectious disease research labs work on finding a cure for a particular disease. Whether it be developing new drugs against a particular pathogen, these types of labs lean more toward what is called ‘translational research’ labs.

This type of research uses the knowledge gained from clinical trials and fundamental research to come up with new treatments, procedures and tools to help patients.

These labs may pop up more prominently in the media as they interact directly with the community at large and their work would make a big, and much more immediate, impact to society.

What I work on is completely different to this.

My work (and my Lab) is predominantly placed in the fundamental research category.

We aren’t particularly interested in finding a cure for our bacterial pathogen, Coxiella burnetii.

Sure, it causes a human disease called Q fever, it can cause debilitating chronic fatigue, and it was once studied as a potential bioterrorism weapon during the Cold War… but while those are all interesting points, the reason we work on this pathogen is a lot more nitty gritty than that.

Coxiella is quite fascinating to us as it is the only bacterial pathogen (that we know of) to require the host lysosomal compartment for replication.

The lysosome, for those that aren’t aware, is like the recycling bin within our cells. Every cell needs a bin- you can use it to recycle your own material to re-use in other parts of the cell, or you can use it to destroy invading pathogens like bacteria.

It’s a highly acidic environment where most living things are obliterated… unless you’re Coxiella. Other bacterial pathogens, like Legionella pneumophila, the causative agent of Legionnaire’s disease and the closest relative to Coxiella, actively escape being degraded in the lysosome.

They will purposefully inject their own bacterial proteins into the host cell to hijack and control the cell, and avoid being placed in that recycling bin. Coxiella, on the other hand, actually allows the host cell to traffic them to the lysosome.

Just sits there, patiently waiting to be placed in this extremely harsh and typically inhospitable environment.

Now, I think many people forget that bacteria, much like us, needs food to survive. Coxiella is no exception, and they’ve adapted their metabolism to scavenge nutrients from their host cell.

Why waste energy making nutrients when you can just steal it from your environment? Especially when said environment is the recycling bin of the host cell. Plenty of nutritious material already broken down to their basic components by the host cell, free of charge.

Our recent work has been able to show that Coxiella are quite good at this food scavenging. So much so that they can adapt to their surroundings and eat what they can find.

For instance, when they’re grown inside the human cell, they tend to eat amino acids, the breakdown product of proteins, which are found in high amounts within the host lysosome.

When you change this environment, and the availability of each nutrient is different, they seem to be able to switch to what is more abundant.

So, when the bacteria are grown outside of the cell in a sugar-rich, liquid environment, they seem to eat sugars more readily than amino acids.

They even have at least two dedicated transport proteins to take in and use glucose to generate energy, which suggests to us that while they like their proteins, they also have a bit of a sweet tooth.

Being a fussy eater as an invading pathogen would be very disadvantageous for Coxiella, so it makes sense that they have the ability to use whatever they can get their hands on to survive and replicate inside the host recycling bin.

Quite successfully, in fact, because at their most active state, they grow so much that the bacteria containing compartment takes up almost all of the space inside the host cell.

Sure, our work won’t immediately cure people from a Coxiella infection, but understanding how pathogens interact with their hosts is absolutely fascinating.

Perhaps if we find a metabolic pathway that is unique and essential for Coxiella to grow inside our cells, we could come up with ways to knock out that system and kill or stop the bacteria in its tracks, but… sometimes just knowing how stuff works is what drives people to work their hearts out.

I think of basic research like this. It’s a piece of the puzzle in a giant jigsaw.

Maybe the jigsaw is for a cure. Maybe it’s to understand how the world around us works. Either way, the puzzle will never be complete without that unique piece.

One single piece doesn’t necessarily have the impact to complete the picture, but it will definitely add to existing knowledge.

Maybe one day, all the pieces will fit and something amazing will come out of it, but until then, all we can do is keep putting all the pieces together… unfortunately without any idea of what that picture might look like, but still, we keep working.

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