MicrobiologyBytes

Since ancient times, Yersinia pestis has wreaked havoc on the human population. In this article in Microbiology Today (pdf) Petra Oyston asks what can the transmission and evolution of this unusual pathogen teach us about how we might prepare for future emergent pathogens?

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Several historical epidemic waves of plague have been attributed to Yersinia pestis, the etiologic agent of modern plague. The most famous of these was the second pandemic which was active in Europe from AD 1347 until 1750, and began with the ‘Black Death’. The most informative method to establish the etiological nature of these ancient infections should be the analysis of ancient DNA, but the results of this method have been controversial. By combining ancient DNA analyses and protein-specific detection, this paper demonstrates that Y. pestis caused the Black Death. Furthermore, they show that at least two variants of Y. pestis spread over Europe during the second pandemic. The analysis of up to 20 diagnostic markers reveals that the two variants evolved near the time that phylogenetic branches 1 and 2 separated and may no longer exist. These results resolve a long-standing debate about the etiology of the Black Death and provide key information about the evolution of the plague bacillus and the spread of the disease during the Middle Ages.

Distinct Clones of Yersinia pestis Caused the Black Death. PLoS Pathog 6(10): e1001134. doi:10.1371/journal.ppat.1001134
From AD 1347 to AD 1353, the Black Death killed tens of millions of people in Europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18th century. The etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by Yersinia pestis to conclusions that it must have been caused by other pathogens. It has also been disputed whether plague had the same etiology in northern and southern Europe. Here we identified DNA and protein signatures specific for Y. pestis in human skeletons from mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. We confirm that Y. pestis caused the Black Death and later epidemics on the entire European continent over the course of four centuries. Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route. These two clades are ancestral to modern isolates of Y. pestis biovars Orientalis and Medievalis. Our results clarify the etiology of the Black Death and provide a paradigm for a detailed historical reconstruction of the infection routes followed by this disease.

Related:

• Ancient Plague
• Plague: Past, Present, and Future
• Plague: From the 14th to the 21st century and still going strong

Arthropod-borne transmission of bacterial pathogens is somewhat rare but has evolved in a phylogenetically diverse group that includes the rickettsiae, Borrelia spirochetes, and the gram-negative bacteria Francisella tularensis and Yersinia pestis, the plague bacillus. Y. pestis circulates among many species of wild rodents, its primary reservoir hosts, via flea bite. As it alternates between fleas and mammals, it is postulated that Y. pestis regulates gene expression appropriately to adapt to the two disparate host environments, and that different sets of genes are required to produce a transmissible infection in the flea and disease in the mammal. Many important Y. pestis virulence factors that are required for plague in mammals have been identified, and most of them are induced by a temperature shift from <26°C to 37°C, which mimics the transition from a flea to the warm-blooded host. To date, only three transmission factors (genes specifically required to produce a transmissible infection in the flea) have been characterized.

Bubonic plague cycles depend on the ability of Y. pestis to alternately infect two very different hosts – a mammal and a flea. Like any arthropod-borne pathogen, Y. pestis must sense host-specific environmental cues and regulate gene expression accordingly to produce a transmissible infection in the flea after being taken up in a blood meal, and again when it exits the flea and enters the mammal. Researchers examined the Y. pestis phenotype at the point of transmission by in vivo gene expression analyses, the first description of the transcriptome of an arthropod-borne bacterium in its vector. In addition to genes associated with physiological adaptation to the flea gut, several Y. pestis virulence factors required for resistance to innate immunity and dissemination in the mammal were induced in the flea, suggesting that the arthropod life stage primes Y. pestis for successful infection of the mammal.

Transit through the Flea Vector Induces a Pretransmission Innate Immunity Resistance Phenotype in Yersinia pestis. 2010 PLoS Pathog 6(2): e1000783. doi:10.1371/journal.ppat.1000783

Related:

• Plague: From the 14th to the 21st century and still going strong
• Plague: Past, Present, and Future
• A bacteriophage contributes to the pathogenicity of the plague bacillus

On Sunday BBC World Service emailed me to ask about the outbreak of pneumonic plague in China (latest news). Unfortunately, I didn’t get the email until today, but for BBC World Service (and everyone else), here are:

10 Things You Should Know About Pneumonic Plague

1. Plague is caused by the Gram-negative bacterium Yersinia pestis.
2. Most forms of plague, such as bubonic plague, are transmitted from the animal host (usually a rodent) by insect vectors such as fleas.
3. In bubonic plague, patients develop swollen, tender lymph glands (called buboes) and fever, headache, chills, and weakness. Bubonic plague does not spread from person to person.
4. Pneumonic plague is the least common but most dangerous and fatal form of the disease.
5. Pneumonic plague is transmitted directly from one person to another by aerosols.
6. Infected people usually get “flu-like” symptoms after an incubation period of 3 to 7 days, with fever, chills, head and body-aches, vomiting and nausea.
7. Yersinia pestis infections are relatively easily treated with antibiotics.
8. Peumonic plague is very virulent, so treatment needs to start early to prevent serious illness or death – within hours of symptoms starting.
9. Although you might think of plague is a disease of the middle ages, it hasn’t gone away – it still occurs in many countries in Africa, the former Soviet Union, the Americas, and Asia. Previous outbreaks of pneumonic plague have occurred in Africa, India, and elsewhere. African countries accounted for nearly 90% of the 28,530 plague cases reported to the World Health Organization from 1994-2003 (Bubonic and pneumonic plague – Uganda, 2006. MMWR 2009 58(28): 778-781).
10. A safe and effective pneumonic plague vaccine would prevent future outbreaks and thwart the use of Y. pestis as an agent of terror. Unfortunately, over 100 years of research have yet to generate a safe and effective pneumonic plague vaccine (Current challenges in the development of vaccines for pneumonic plague. Expert Rev Vaccines. 2008 7(2): 209-221).
11. Should I be worried about this outbreak?
    No, not particularly. This outbreak is in an isolated region and the Chinese authorities have taken appropriate steps to contain it. I would have been much more worried if it had occurred in a metropolitan region such as Beijing or Shanghai.

Related:

• How plague bacterium Yersinia pestis damages eukaryotic cells
• Plague: From the 14th to the 21st century and still going strong
• Ancient Plague
• Plague. Br Med Bull. 1998 54(3): 625-633
• Epidemiologic determinants for modeling pneumonic plague outbreaks. Emerg Infect Dis. 2004 10(4): 608-614
• Immune defense against pneumonic plague. Immunol Rev. 2008 225: 256-271