Thursday, August 19, 2010

We are often collateral damage

In a recent post, Ed Yong (Not Exactly Rocket Science) describes the concept of "coincidental evolution" of certain bacterial species that are virulent in people.
If you’re trapped in a building, it’s probably not the best time to start setting fire to things. But this is exactly what some bacteria do when they find themselves in a human; they cause diseases that are potentially fatal but not contagious. Without an escape, they risk going down with their host. This seems like a ludicrous strategy but we’re looking at it from the wrong perspective – our own. In truth, humans often have nothing to do with the diseases that plague us; we’re just collateral damage in an invisible war.

Like all living things, bacteria have to defend themselves against predators like amoebas. Some species do so using resistance genes that turn them from passive victims into aggressive fighters. And by coincidence, these same adaptations make them more virulent (good at causing disease) in human bodies. We’re just caught in the crossfire."

(From "Disease by coincidence – why we’re caught in the crossfire of a hidden war" | Not Exactly Rocket Science | Ed Yong | Discover Magazine)

He discusses several examples of species that appear to have evolved mechanisms to defend against or escape natural predators in their environmental niche.These predators include amoebas (Escherichia coli, Legionella pneumophila), where resistance to grazing or the ability to survive engulfment allows the bacteria to do the same thing with regards to macrophages in a human host. Another example is when normally harmless Streptococcus pneumoniae becomes infectious for humans after it is exposed to Haemophilus influenzae; evidently this exposure induces the former to produce a thicker capsule that makes the bacterium resistant to the human immune system.

I've thought about this concept of "accidental virulence" for quite some time. One of the pathogens I work on, Vibrio parahaemolyticus, forms an extremely diverse species, with a highly plastic genome. This variability can be explained in part by the large number of mobile genetic elements and bacteriophage remnants, as well as the ability to take up and incorporate exogenous DNA by transduction, conjugation, and transformation. Yet when isolates from clinical infections are examined by methods such as multilocus sequence typing, these 'by definition' virulent strains appear to be part of a small number of highly clonal complexes. The normal environmental niche of these bacteria is in estuarine marine waters, where they are found free swimming or colonizing a variety of biotic (copepods, zooplankton, phytoplankton, shellfish) and biotic (anything with chitin) surfaces.

For years virulence of this and related species have been studied by classical molecular pathogenesis methods, i.e., find a suspect virulence gene, knock it out, and look at changes in the mutant's ability to do something to an experimental host, tissue cell line, etc. Yet in my opinion none of these studies have developed a method to truly say that a given strain will be virulent and highly capable of causing disease. These are opportunistic pathogens, so it seems to make sense that the few strains capable of infecting and causing pathology in humans have actually developed or adapted new ways to survive and/or proliferate in their environment, perhaps in response to changes in local environmental factors. It just so happens that these adaptive changes make them more virulent, maybe increased survival in stomach acid, enhanced colonization of the gut epithelium, or secretion of extracellular enzymes or toxins we don't yet know about.

All reasons why I'm very anxious about getting my genome sequencing project off the ground!

Sunday, May 23, 2010

Genomics here we come

It's been a very busy first 6 months of 2010, with much of my time focused on doing "other" things critical for my job, and to the center/agency programs. Unfortunately these time consuming activities have considerably slowed my ability to push some of the lab science forward. It didn't help that the post doc I had who was working on the genomics project left to take an internship with another government agency. This was good for him and important for his future aspirations, it paid him considerably more, and I felt I really had to encourage him to take it. But it sure caused a loss of momentum, and with the time commitment needed for his internship, I don't see him writing up one of his two projects unless I try to draft it.

However, unless I am requested to provide research support for a microbial perspective on seafood safety or ecological damage assessments as a result of the Gulf of Mexico Transoceanic oil spill disaster, things should start heating up this summer. I have a new post doc coming in July who will drive the genomics work. A couple of months ago he spent 4 weeks in the lab on an internship (funded through one of the national programs that my program is a part of), and I was both impressed and relieved that he will prove to be one of the better ones.

Everything's in place, financially and organizationally, to have 10-16 strains of my favorite bacterial species sequenced to ~100x coverage on a SOLiD next gen sequencer (when do they become current gen?). Strains to be sequenced have already been subjected to MLST analysis, clonal groups characterized and relationships established. The objectives include determining what is different at the genome level between clinical (therefore virulent) strains, which form one tight clonal complex and appear rare in the environment, and other environmental isolates that belong to other phylogenetic groups and are not isolated from clinical cases.

This should be fun, and I do need some of that at work!

...staying put

It's been a long time since I last wrote here, and I just realized I never did post the outcome of my candidacy for a marine genomics faculty position (discussed earlier here).

Obviously, it wasn't me who was selected. I probably would have written about that. After almost 10 months of waiting, the med school dean/committee picked a very accomplished researcher, big research group, Howard Hughes Professor, ~250 publications, yada, yada. Really, I was flattered to be recruited to apply, and then asked to interview; then to make it as a top 3 candidate was icing on the cake. But from what what I know about the person selected, and what I've heard from others associated with both the university and the government lab where the person's research group will be based, it was kind of a strange selection. His background and career, while stellar, did not really fit the requirements and qualifications that were originally advertised. I'm not trying to sound bitter, because I'm not, and I realize shifts in positions happen. I've also heard that restructuring at the school might have made it less attractive to make the jump for someone like me.

So, as far as I know, I'm not going anywhere. I have several good years left, so I'm finally acting on some opportunities to make some changes in my work situation, plus I'm now more determined to follow through on many of the goals for the research I've set.