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Yersinia pestis, the plague bacillus, has an exceptional pathogenicity but the factors responsible for its extreme virulence are still unknown. A genome comparison with its less virulent ancestor Yersinia pseudotuberculosis identified a few Y. pestis-specific regions acquired after their divergence. One of them potentially encodes a prophage (YpfPhi), similar to filamentous phages associated with virulence in other pathogens. YpfPhi forms filamentous phage particles infectious for other Y. pestis isolates. Deletion of the YpfPhi genome does not affect Y. pestis ability to colonize and block the flea proventriculus, but results in an alteration of Y. pestis pathogenicity in mice. Transformation of Y. pestis from a classical enteropathogen to the highly virulent plague bacillus was accompanied by the acquisition of an unstable filamentous phage. Continued maintenance of YpfPhi despite its high in vitro instability suggests that it confers selective advantages to Y. pestis under natural conditions. This study represents the first characterization of a chromosomal element acquired by Y. pestis after its emergence from its recent ancestor Y. pseudotuberculosis and which may have participated in its evolution towards a deadly pandemic pathogen.

A horizontally acquired filamentous phage contributes to the pathogenicity of the plague bacillus.
Mol Microbiol. 2007 63: 1145-1157.

Related:

• Ancient Plague
• How plague bacterium Yersinia pestis damages eukaryotic cells
• Plague: From the 14th to the 21st century and still going strong

Clostridium botulinum is a heterogeneous Gram-positive species that comprises four genetically and physiologically distinct groups of bacteria that share the ability to produce botulinum neurotoxin, the most poisonous toxin known to man, and the causative agent of botulism, a severe disease of humans and animals. We report here the complete genome sequence of a representative of Group I (proteolytic) C. botulinum. The genome consists of a chromosome (3,886,916 bp) and a plasmid (16,344 bp), which carry 3650 and 19 predicted genes, respectively. Consistent with the proteolytic phenotype of this strain, the genome harbors a large number of genes encoding secreted proteases and enzymes involved in uptake and metabolism of amino acids. The genome also reveals a hitherto unknown ability of C. botulinum to degrade chitin. There is a significant lack of recently acquired DNA, indicating a stable genomic content, in strong contrast to the fluid genome of Clostridium difficile, which can form longer-term relationships with its host. Overall, the genome indicates that C. botulinum is adapted to a saprophytic lifestyle both in soil and aquatic environments. This pathogen relies on its toxin to rapidly kill a wide range of prey species, and to gain access to nutrient sources, it releases a large number of extracellular enzymes to soften and destroy rotting or decayed tissues.

Genome sequence of a proteolytic (Group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes. Genome Research, DOI: 10.1101/gr.6282807

On 9th December 1979, the W.H.O. officially declared smallpox to be completely eradicated. This was not quite correct, since the United States and Russia, hold the only known stockpiles of the virus in high-security laboratories. Both countries have long resisted calls to destroy them in case smallpox is found to exist elsewhere, and the events of September 11th 2001 did not encourage either country to get on with it and finally rid the world of this scourge.

On Friday, the 60th annual World Health Assembly, the top decision-taking body of the W.H.O., reaffirmed a previous commitment to getting rid of the remaining stockpiles but agreed to postpone any decision on when this should happen until its 2011 meeting.

A dose of the pox: An interactive tutorial that steps you through the discovery & ultimate eradication of smallpox using a series of questions.

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When I say the word pandemic, you probably think first of influenza, and in the present circumstances, that’s quite understandable. But in addition to viruses, other micro-organisms also show pandemic patterns of infection, i.e. an outbreak of an infectious disease which spreads across a large region, or even worldwide. Cholera is an example of a bacterial disease which spreads widely, and seven cholera pandemics have been identified, with the first beginning at the start of the nineteenth century and most recently with the seventh pandemic in the 1960s. However, the most obvious micro-organism which spreads in a pandemic manner is of course plague. MicrobiologyBytes listeners are a bloodthirsty bunch, and whenever I’ve talked about plague before, it’s caused a big response, so hopefully you’ll enjoy this story too!

The first known pandemic of plague was the Plague of Justinian which started around A.D. 540 and clearly shows the symptoms of bubonic plague. The best known plague pandemic was of course the Black Death, which swept across Eurasia in the mid-14th century, killing approximately one third of the population according to some estimates. The third plague pandemic began in China in 1855 and spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone. According to the World Health Organization, this pandemic was considered active until 1959, when worldwide plague casualties dropped to 200 per year.

Until recently, the history of bubonic plague has been left to historians and archaeologists. Although historical descriptions of the first and second plague pandemics certainly sound like they were caused by Yersinia pestis, the bacterium which causes plague, that’s not scientific evidence. Now, thanks to a paper just published in Emerging Infectious Diseases, we finally have the science to back up the history.

Previous studies which attempted to detect Yersinia pestis 16S rDNA from teeth collected from human remains in seven northern European sites were negative (Gilbert M. et al. Absence of Yersinia pestis-specific DNA in human teeth from five European excavations of putative plague victims. Microbiology. 2004;150:34154).

Biochemical characterization shows that there are four distinct biotypes of Yersinia pestis: Antiqua, Medievalis, Orientalis and Microtus. Historical evidence indicated that three mass graves excavated in France had been used to bury bubonic plague victims. By carbon-14 dating and from finds such as coins as well as historical documents, it was known that the people examined had died between the 7th-9th centuries and in May 1722, so the specimens covered all three plague pandemics.

DNA was extracted from the teeth of skeletons and the Yersinia pestis glycerol-3-phosphate dehydrogenase gene was amplified by PCR. Since this gene is the basis for the biochemical differences between the biotypes of Yersinia pestis, this study not only confirmed that this organism was indeed responsible for all three plague pandemics, but also showed that it was the Orientalis biotype which was involved.

Now if you’re a historian or an archaeologist, you might be pretty excited by this, but if you live in the present rather than the past, you might be asking yourself, so what? Well as I mentioned in a previous podcast plague hasn’t gone away, and climate change might make it more of a problem in the future than it has been recently. As if that wasn’t bad enough, plague has a long history as a biological weapon, with stories of infected animal carcasses being used to contaminate enemy water supplies, and human corpses being tossed by catapults into cities under siege. More recently, Yersinia pestis has been weaponised, with both the United States and the Soviet Union developing means of producing and delivering antibiotic-resistant pneumonic plague. So if you’re mildly interested in staying alive, you may want to consider what the history geeks have to tell us about pandemic plague, and think about what we should be doing to prevent future outbreaks.

• Drancourt M, Signoli M, Vu Dang L, Bizot B, Roux V, Tzortzis S, et al. Yersinia pestis Orientalis in remains of ancient plague patients. Emerg Infect Dis 13 (2) February 2007.

A while ago I wrote about the vulnerability of food supplies to possible bioterrorist attacks. While there’s absolutely no evidence that the recent North American spinach-related E. coli outbreak has anything to do with terrorism, it is a prime example of how vulnerable centralized, industrialized food supplies are to contamination, whether accidental or deliberate. It’s also a good example of the capacity of E. coli, the bug we thought was so friendly (I get a lot of hits when I blog about “friendly bacteria”!) can turn around and bite us.
Wash that spinach, and wash your hands!

• Podcast: E. coli O157:H7 Spinach Outbreak
• Latest News

As I described in this week’s podcast, Plague: From the 14th to the 21st century and still going strong, Yersinia pestis has been a major human pathogen for many centuries, and with climate change, looks set to get even worse. Part of the problem is that we still don’t have a really good understanding of how this bacterium causes disease. A paper just published in the journal Cell goes a long way towards changing that.
A critical virulence determinant in Yersinia species is the Yersinia protein kinase A, YpkA, a multidomain protein which disrupts the actin cytoskeleton in eukaryotic cells, essentially the glue which holds cells together. Despite its known importance to virulence, little has been forthcoming in understanding the mechanism of activity of YpkA. The new paper shows that YpkA possesses a Rac1 binding domain which mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases, so virulence in Yersinia species depends upon mimicry of host GDI proteins by YpkA. The new data strongly suggests that YpkA mimics host GDI proteins by acting as an “off switch” to modulate the Rac1-associated signaling pathways that regulate host cytoskeletal structure.
The authors also point out that it is becoming increasingly clear that mimicry of eukaryotic biochemical processes is a common strategy used by many bacterial pathogens to modulate host cell biology, something that might previously only have been ascribed to viruses.

• Prehna, G. et al. Yersinia Virulence Depends on Mimicry of Host Rho-Family Nucleotide Dissociation Inhibitors. 2006 Cell 126: 869-880.

Plague tomb in Eyam by martsky

The Black Death, also known as the Plague, was a devastating pandemic that struck Europe in the 14th century, and killed between a third and two thirds of Europe’s population. Almost simultaneous epidemics occurred in Asia and the Middle East during the same period, so the well recorded waves of infection in Europe were really part of a worldwide pandemic which killed at least 75 million people. The same disease is thought to have returned to Europe every generation with varying degrees of severity until the 1700s. The disease was completely eradicated in Europe only at the beginning of the 19th century, but survives in other parts of the world, notably in Africa, Asia and the Americas — including the United States.
But Yersinia pestis, the bacterium which causes plague, has not gone away, and climate change could mean that worse is to come. Find out more in this week’s MicrobiologyBytes podcast:

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Links:

• Wikipedia: The Black Death
• Wikipedia: Eyam
• CDC Plague Home Page
• Achtman M, et al. Microevolution and history of the plague bacillus, Yersinia pestis. PNAS USA. 2004 101: 17837-42.
• Chr Stenseth N, et al. Plague dynamics are driven by climate variation. Proc Natl Acad Sci USA. 2006 Aug 21.
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