Sequencing done, finally!

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!

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!

One Health

A few months ago I was asked to write a paragraph describing the One Health Paradigm for a regional white paper on the regional marine ecosystem. This is what I came up with, heavily borrowing from several sources. It has become a useful way for me to describe the the multifaceted approach I'm moving my lab's research toward. Specifically, an approach that includes the role of environmental factors (abiotic and biotic), human factors (health status, habits, etc.), and pathogen genetic factors, in order to understand why only a small number of strains of a given species of a marine bacterium are truly virulent.

The One Health Paradigm reflects the inter-relationships between environmental, animal, and human health. The One Health Approach for improving human health is equally applicable to terrestrial and aquatic environments. Of the 1,461 infectious diseases now recognized in humans, approximately 60% are due to multi-host pathogens characterized by their movement across species lines. Over half of all new or emerging infectious diseases since the 1940s have jumped from domestic and wild animals to humans, and it is fully expected that this trend will continue. Anthropozoonoses, diseases that effect both animals and humans, often result in animals serving as reservoirs for re-emerging or new diseases. Environmental degradation through pollution and contamination, or changes in the environment brought about by climate change, may result in favorable settings for expansion of existing infectious diseases, may increase the transmissibility of these diseases, or may lead to altered patterns of pathogen virulence as they rapidly adapt to new environmental cues. Animal and human migration patterns also shift in response to climate change, further leading to new routes of exposure. Therefore, to fully understand, forecast, and control emerging infectious diseases requires an interdisciplinary and holistic approach that combines the studies of pathogens and their virulence, animal health and zoonoses, and the role of climate change and other factors on environmental health. While the One Health approach is often used in context for the control of infectious disease, the paradigm is easily extended to include an understanding of the fate of contamination of the environment with a variety of chemicals, fertilizers, and antibiotics. These anthropogenic factors have both direct and indirect impacts on human health. In all cases, the One Health approach is aided by the incorporation of the concept of sentinel species, including the acquisition of pathogens infectious to humans as well as the impacts of chemical contaminants on development, reproduction, and overall health.

References:

King, L. (Ed). One Health: A New Professional Imperative. One Health Initiative Task Force, American Veterinary Medical Association (2008) pp. 1-76

King, D. A., C. Peckham, J. K. Waage, J. Brownlie, and M. E. J. Woolhouse. Infectious diseases: preparing for the future. Science (2006) vol. 313 (5792) pp. 1392-3

Torrey E. F., and Yolken R. H. Beasts of the Earth. New Brunswick, NJ: Rutgers University Press (2005).

other

2009 ASM General Meeting symposium description: "One Health - A New Paradigm for Microbiology and Public Health" (May 19, 2009)

MicrobeWorld (video of ASM press conference for same symposium)

Someone (and I can't remember who and where) used this image to describe how changing migration patterns of animals and humans contribute to new infectious disease spread.

Comments welcomed.