Turned up to eleven: Fair and Balanced

Tuesday, March 07, 2006

Connecting environmental microbiology to the "important stuff"

I was perusing the wonderful blogs hosted by Seed Magazine (all of 'em are great, but Frinktank is clearly a rising star!) when I saw a new microbiology paper(subscription req'd) noted by Afarensis. The paper is about MRSA (Methicillin Resistant S. aureus) being shown to persist inside amoeba. I argued, hopefully justifiably, that you can artificially create a situation like this in many systems, and we shouldn't all run for the hills yet. Unfortunately, I haven't had a chance to read the paper (never stopped me before!), but I have to suspect that they would acknowledge my simple, naive criticism, and either deal with it experimentally, or simply admit that it needs to be studied further. Either is a very reasonable tack. I suspect someone smarter, more capable, and with better institutional access will do the thorough once over of this paper, so I'll tackle a larger question. Why would bacteria want to be able to do this, and why would it be important to us?

Because I am just not up to a long exposition, I'll tease you a bit with this, and hopefully get some comments. We know that many pathogens are highly adapted to life in the animal, plant or human host. We also know that one of the major obstacles to persistence and infection is the innate immune system, consisting of humoral responses (complement) and cellular responses (neutrophils and macrophages, cells that eat bacteria). Note, for the immunologists, that there are two analogous branches of adaptive immunity, and based on evolutionary analysis, it is thought that the innate system developed much earlier, and the adaptive system piggybacks on it (I'm simplifying here!!).

There are a lot of complex things going on in pathogenesis, some of which I've alluded to before. A major part of the process is resisting the immune response, both innate and adaptive. We'll leave the adaptive system for now, and focus on the innate system. The big danger to any invading bug is that a phagocytic cell (like I mentioned above) will eat it. So, many mechanisms for evading this response have evolved. A big one is the ability to persist in the endocytotic vesicle (depending on the cell, the endosome or the phagosome). The phagocytic cell has a vesicle called a lysosome that fuses with the phagosome to make, unsurprisingly, a phagolysosome. This fused vesicle contains acid and lytic enzymes to break the bacterium down. Defenses against this fusion, resistance to these enzymes, and acid tolerance are all great ways for bacteria to avoid this fate. In pathogenic systems, some classic examples of these mechanisms are found in Mycobacterium tuberculosis, Listeria monocytogenes, and Legionella pneumophila.

So what? Well, it turns out that each one of these bacteria have close relatives that live in natural environments inside amoeba and other phagocytic protozoa. A good review (that I just found and should read!) by Jorge Galan gives info about this and other commonalities between environmental persistence and infection. So, here's the $64,000 question (and I pose it honestly as well as rhetorically); Did bacteria already well adapted to life in soil, battling for nutrients and fighting off eukaryotic predators (protozoans, fungi) evolve all of their mechanisms in that environment, and then adapt them to colonizing and infecting eukaryotes? It's a reasonable hypothesis, and the rough time frames of the rise of various types of eukaryotes and bacterial divergences are reasonably congruent with it (note, I'm no expert on the time scales of branching events in microbial phylogeny; any knowledgeable parties should please comment).

So, here I'll leave you with the big challenge. How do we gather evidence to support or invalidate this hypothesis? Can you plan out an experimental scheme to understand this system?

Obligatory anti-ID snark; no fair just saying "God did it"!
Second anti-ID snark; there is simply no rational way to understand how different pathogenic bacteria attack many different hosts in fundamentally similar ways without acknowledging the role of evolution by variation and natural selection)