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The bug that lost a few genes to become Black Death

About 6,000 years ago, a bacterium underwent a few genetic changes. These allowed it to expand its habitat from the guts of mice to that of fleas. Such changes happen all the time, but in this particular…

Not pretty. Pete Seidel/Jack Poland/CDC

About 6,000 years ago, a bacterium underwent a few genetic changes. These allowed it to expand its habitat from the guts of mice to that of fleas. Such changes happen all the time, but in this particular instance the transformation eventually resulted in the Black Death that wiped out a third of Europe’s population in the 14th century.

Yersinia pestis (YP), which causes plague, evolved from an ancestral bacteria called Yersinia pseudotuberculosis (YPT). This happened somewhere in China, from where it spread westward causing disease in both animals and humans. In a new study, published in the journal Cell Host & Microbe, researchers at the National Institute of Allergy and Infectious Diseases have retraced the genetic changes that enabled this bug to become one of the most feared microbes.

Making the switch

Infections due to both YPT and YP are classified as “zoonoses”, transmissible from animals (mainly rodents) to other animals, including humans. YPT is transmitted by fecal contamination of food and water. In contrast, the more lethal YP is transmitted via bites of infected fleas.

Genetically, YP possesses a smaller subset of the genes present than its ancestor YPT. And yet, while YPT causes a relatively mild disease in various mammals, YP causes types of plague – a severe, inflammatory disease that may be fatal if left untreated.

When a microbe evolves into a more potent agent of disease, the usual reason is the addition of genes (for example, genes that make a bug resistant to antibiotics). But, according to Yi-Cheng Sun and colleagues, the YPT-to-YP switch involved both addition and removal of genes, resulting in a net loss.

Sometimes, a microbe in a given environmental niche undergoes changes in its genetic make-up. These changes come in four types:

  1. neutral – has no effect
  2. deleterious – renders the surrounding environment inhospitable, causing it to die or move to a new niche
  3. allows adaptation – minor change to suit the new environment
  4. increase fitness – confers the ability to exploit the new niche to thrive

Adaptive genetic changes (such as numbers 3 and 4) may thus establish a new habitat for the organism, and may lead to the emergence of a new species. Ecologists call this process adaptive radiation. However, not all the key genetic mechanisms involved in this process are currently well-understood.

Nonetheless, adaptive radiation likely explains the changes YP underwent to become highly infectious. Sun and colleagues present convincing evidence that adaptive genetic changes in YP – involving the loss of three genes and gain of one – allowed it to thrive in the flea internal environment as compared to YPT.

YPT, ingested by a rodent, lives peacefully in its gut, until there are enough of its brethren or the host’s immunity falls. When that happens, YPT slips into the rodent’s bloodstream. Fleas, living on the rodent, happily suck in the bug-laden rodent blood. Inside the flea, a sticky protein that YPT makes allows it to set up home in the hindgut (lower digestive tract) without causing disease. It is then regularly shed through the flea’s feces.

Flea master

YP lacks the ability to make that sticky protein. This means that it cannot live in the hindgut like YPT. Interestingly, the only gene YP gained allows it to sit instead in the midgut and foregut of the flea, closer to the mouth.

YP is able to do this by covering the flea gut surfaces with a polymeric biofilm in which it remains embedded. YPT cannot do this because three genes suppress this ability. Incidentally, these are the three that YP lost, thereby gaining this function. The biofilm allows YP to remain in the flea (when YPT is removed with feces). This, along with the gut positioning, increases YP’s chances of transmission to a new host via flea-bite.

YP infection – via rodent hosts and flea transmission – continues to occur sporadically in some parts of the world, such as Africa, Western South America, the Western United States, and parts of Asia. But there is evidence that YP may be losing further genes, reducing its disease-causing potential. Besides, modern antibiotics can treat such plague-type infections.


Next, read this: Study finds widespread antibiotic resistance in nature

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10 Comments sorted by

  1. Paul Richards

    integral operating system

    Appreciate the article.
    It does raise questions about bacterium adaptation to global warming and subsequent climate change in our era. One that comes to mind; wIll higher species extinction be accelerated if adaptive genetic change in bacterium contribution ecosystems become weighted?
    From this perspective how fast and how extensively bacterium adapts is integral to all life on earth as we know it. For the first time in written history humans are able study life on earth in detail, it is interesting how crucial this ability is with relatively rapid environmental change.

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    1. Kausik Datta

      Post-doctoral Fellow at Johns Hopkins Medicine

      In reply to Paul Richards

      Thank you for your thoughtful comment. In any host-pathogen interaction, the important contribution of a third component - the environment - is now increasingly being recognized. Anthropogenic climate change, particularly the slow rise of global climatic temperatures, may indeed change global microbial habitats with corresponding repercussions on the environment. It is likely that under such conditions - especially when there is adversity - adaptive genetic changes may confer upon the microbes an enhanced ability to survive in inhospitable environments, and therefore increase their pathogenic potentials. However, it should be borne in mind that these changes may sometimes take thousands of years to be stably established in a microbe.

      That said, I admit freely that I don't have a ready answer to your question, but I appreciate its depth.

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    2. Paul Richards

      integral operating system

      In reply to Kausik Datta

      Appreciate the reply and enjoy reading your articles.
      Kausik Datta wrote;" ... that I don't have a ready answer to your question" It was a loaded question and was made more to jar others thinking.
      My area of interest is futurist, currently rebranded as strategic foresight in deference to the lens focusing on economics. The worldview is different to most, so understand questions that others don't ask or can't.
      Having said that, there is a serious case for funding of the study of emerging pathogens…

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  2. Henry Haszler

    Economist

    I know the article is about genetics but, still, why nothing in this Conversation article about the recently breaking research suggesting that the spread of the black death in London was airborne.

    It seems the spread by the so far accepted rats fleas route could not have explained the speed of the spread whereas coughing in the crowded conditions of London could explain it.

    The URLs, using the tinyurl system, to two articles in the British press are at:

    http://tinyurl.com/Guardian-Plague
    http://tinyurl.com/DailyMail-Plague

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    1. Kausik Datta

      Post-doctoral Fellow at Johns Hopkins Medicine

      In reply to Henry Haszler

      _"I know the article is about genetics but, still, why nothing in this Conversation article about the recently breaking research suggesting that the spread of the black death in London was airborne."_

      Precisely because the article under discussion was about genetics and fitness of Yersinia pestis in a given environment.

      That said, I would like to address the point you raised by urging caution about interpretations of studies in news reports and press releases.

      Suffice it say, it is not…

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  3. Bjørn Østman

    logged in via Facebook

    Two quibs:

    You list four kinds of mutations, but in this scheme there are only really three: neutral, deleterious, and beneficial. The third kind you mention is either neutral or beneficial. I assume you are thinking about an epistatic mutation, but if so, that mutation is either neutral or beneficial in a given environment. Deleterious mutations also do not necessarily cause an organism to die or move to a new niche (not sure what you mean by the latter - a niche is not a geographic location). Many organisms survive with deleterious mutations.

    When one species adapts to a new environment we do not call it adaptive radiation. For that to be said to occur organisms have to (rapidly) diversify into multiple lineages. Also, it is really a term from evolutionary biology rather than ecology.

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    1. Kausik Datta

      Post-doctoral Fellow at Johns Hopkins Medicine

      In reply to Bjørn Østman

      I appreciate your points, Bjørn. You are right about there being three kinds of mutation. However, while trying to write a lay language description, I found it easier to describe the four situational outcomes of those mutation types. This is actually how the authors of the original paper (under discussion) describe it, too.

      The description of the deleterious mutation is also to be considered in the given context of Yersinia pestis. It is true that many organisms survive with deleterious mutations…

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    2. Bjørn Østman

      logged in via Facebook

      In reply to Kausik Datta

      As far as I can see there is no mention in the original paper (Sun et al, 2014) that there are four kinds of mutations, like you have laid out. Can you explain?

      Five lineages does indeed qualify it as adaptive radiation, imo. Nice to know that that is what happened. Thanks for clarifying.

      The authors do not say that it is an ecological theory. They say

      "We propose a sequential step-wise model for the evolution of flea-borne transmission in the genus Yersinia ( Figure 6) that conforms to…

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    3. Kausik Datta

      Post-doctoral Fellow at Johns Hopkins Medicine

      In reply to Bjørn Østman

      Not "four kinds of mutations", Bjørn; four kinds of *situational outcomes* from the mutations: (a) neutral in the old environment (mutation does nothing); (b) deleterious in the old environment (mutation reduces fitness in the old environment, may or may not lead to (c) or (d); (c) neutral in the new environment (mutation neither assists nor hinders adaptation); and (d) advantageous in the new environment (mutation actively helps adaptation). I hope I have cleared this up sufficiently now.

      (Oh…

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    4. Kausik Datta

      Post-doctoral Fellow at Johns Hopkins Medicine

      In reply to Kausik Datta

      Sorry, that didn't come out quite right.

      "Oh, and the authors didn't mention these situational outcomes." -- What I mean is that the authors did mention the three types of mutations and their effects in the new and old environment. I mentioned those situational outcomes in order to explain these effects.

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