After several months of waiting, the sequencing run of 20 strains of our favorite species has finally been completed. There were several delays, mostly due to the upgrade of my collaborator's SOLiD sequencer to version 4. In addition there were problems with the emulsion PCR, also due to upgrades. Anyway, in the end it appears we have very good, paired-end sequence data. Preliminary analysis of one of the barcodes suggests we have about 80+% of the reads mapping to the reference genome, with extremely good coverage, about 150x.
Assembly of the 20 strains will commence next week. Then the fun begins, at least for my post doc!
Showing posts with label adaptation. Show all posts
Showing posts with label adaptation. Show all posts
Tuesday, May 10, 2011
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.
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!
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!
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