The Black Death, brought back from the dead
An interesting article, via the New York Times science page this week: scientists at McMaster University (Ontario, Canada) and the University of Tubingen (Germany) have determined the genetic sequence of an isolate of Yersinia pestis, the causative agent of Bubonic Plague. Yersinia pestis is a well studied microorganism, a Gram negative bacterium that is a member of family Enterobacteriaceae, a large group of bacteria that includes the very familiar organism Escherichia coli. Microbiologists have long been puzzled by the fact that current cases of Y. pestis infection seem to be very different from historical cases, leading some historians to suggest that another agent was responsible for causing the Black Death. However, scientists have recently been able to detect the DNA of Y. pestis in exhumed human remains from medieval mass graves, and have now taken that work one step further: they have sequenced the entire genome of bacteria recovered from these remains.
The approach is clever; no living bacteria were recovered from the human remains, and the DNA that remained was rather degraded and fragmented. Consequently, the researchers needed to examine a portion of the remains that might be able to maintain the integrity (as best as possible) of the bacterial samples, and isolated DNA from teeth from the remains for subsequent analysis. One issue however is that the human DNA fragments in the sample would greatly outnumber in complexity the bacterial DNA fragments, making finding the bacterial DNA like finding a needle in a haystack. To overcome this, they used the DNA from a modern isolate of Y. pestis to “fish out” the ancient DNA fragments. This was very successful, and they were able to obtain the complete DNA sequence of the ancient isolate, comprising 4.6 million base pairs of DNA.
The upshot of the DNA sequence of the genome is that only 97 of those almost 5 million base pairs of DNA were altered, and of those only a dozen or so resulted in changes to genes. The researchers are planning on recreating those alterations in a modern isolate of Y. pestis to see if the relative virulence of the organism is altered. They actually do not expect these changes to have a tremendously significant impact on the virulence of the organism, though they do note that it would be handled in an extremely secure facility, and would still be susceptible to antibiotics.
One alternative explanation for the differences between the Black Death then and today might not be in the bacterium, but in the people infected by the organism. Poorer nutrition, lack of public health and sanitation, crowded living conditions, and frequent starvation might have enabled the organism to be more virulent in that population than today’s population. The authors of the Nature article suggest that
these findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.
This is an important point, and reinforces the concept that there is a dynamic interaction between the host and the pathogen, and ANY alteration in that relationship (by the pathogen, or by the host) will cause the process of disease to be different. The graphic to the right very nicely demonstrates that there is a complicated relationship between a pathogen, how the body responds to the presence of that pathogen, and the development of damage to the body. Prediction of virulence and the ability of an organism to cause disease will also need to take into account a myriad of host factors. And the important take home message of this “back from the dead” Black Death is that those factors may be much more important in the long run than aspects of the biology of the organism.
Posted on October 14, 2011, in A bit 'o history, Danger danger danger!, Microbes in the News and tagged Black Death, Bubonic Plague, McMaster University, University of Tübingen, Yersinia pestis. Bookmark the permalink. 1 Comment.