ADVERTISEMENT
  About the SA Blog Network













Guest Blog

Guest Blog


Commentary invited by editors of Scientific American
Guest Blog HomeAboutContact

Like a Game of Clue, Genomics Tracks Outbreak, Revealing Evolution in Action

The views expressed are those of the author and are not necessarily those of Scientific American.


Email   PrintPrint



Photo from CDC. Klebsiella pneumoniae causes severe, hospital-acquired infection. Genome sequencing helped researchers recreate the path of pathogenesis.

Klebsiella pneumoniae causes severe, hospital-acquired infection. Genome sequencing helped researchers recreate the path of pathogenesis. Photo from CDC.

Was it Colonel Mustard in the library with a lead pipe? Or Mrs. Peacock in the ballroom with a candlestick? No, it was deadly, drug-resistant Klebsiella pneumoniae from a 43-year-old woman spreading to 17 other patients, killing 6 of them and sickening 5 others, at the National Institutes of Health’s (NIH) Clinical Center in June 2011.

In a biotech version of the classic board game “Clue,” researchers from the National Human Genome Research Institute (NHGRI) used genome sequencing to solve the medical mystery of how the infection spread. The story, recounted today in Science Translational Medicine, is a fabulous teaming of classic epidemiological sleuthing and genome sequencing of the pathogen. At the same time, the saga glimpses microevolution in action.

K. pneumoniae is one nasty microbe. It kills half of those it infects. It resists many antibiotics, especially in the drug haven that is a hospital, stays alive on the hands of hospital staff, and lives happily in the guts of some people who are unaware that they are infected, even as they unknowingly spread the infection.

These bacteria are so alike genetically that standard ways to type them are useless. Yet changes in their DNA sequences do arise, even in as short a time as the 4 weeks when investigators probed various nooks and crannies of the index case’s body to sample the bacterial genome. They found telltale single gene variants (SNVs, the same as SNPs) at 41 sites in the 6-million-base genome. Some of the variants may have little or no effect, the consequence of a DNA replication error. It happens. But some may reflect the bacterium mutating towards yet another drug resistance. This is the essence of evolution: genetic change over time that affects the phenotype, thereby offering fodder for natural selection.

To deduce who passed the bug to whom, the researchers, with the aid of an algorithm to sort through the possibilities, compared bacterial sequences. “We thought we could use genome sequencing to tell whether the K. pneumoniae from the first patient was the same strain as the one that infected the second patient,” said Julie Segre, who led the team.

The 17 patients fell into 2 groups and one loner. One cluster shared variants with bacteria from the lungs and groin of the index patient (who recovered), another with variants from her throat. The outlier patient got the infection from a contaminated ventilator. To reconstruct these events, because they didn’t connect quite as directly as the suspects in a game of Clue, the researchers sequenced the genomes of all 1,115 patients in the hospital at the time, finding 5 typhoid Marys to fill in the gaps.

And so like the 6 weapons used in 9 rooms of a mansion in the board game, wedding genome sequencing to the who-what-where-when-and-how of an epidemiological investigation can tell infectious disease specialists where to focus their attention.

According to the Centers for Disease Control and Prevention, about 1.7 million people acquire infections in hospitals in the U.S. each year, factoring into 99,000 deaths. “By marshalling the ability to sequence bacterial genomes in real-time to accurately trace the bacteria, our researchers successfully elucidated what happened, which in turn has taught us some important lessons. This study gives us a glimpse of how genomic technologies will alter our approach to microbial epidemics in the future,” said NHGRI Director Eric Green.

Added Segre, “Genome sequencing and analysis is our best hope for anticipating and outpacing the pathogenic evolution of infectious agents. Though our practice of genomics didn’t change the way patients were treated in this outbreak, it did change the way the hospital practiced infection control.”

And provided a compelling example of evolution happening right now.

Reference:

Evan S. Snitkin, Adrian M. Zelazny, Pamela J. Thomas, Frida Stock, NISC Comparative Sequencing Program, David K. Henderson, Tara N. Palmore, and Julia A. Segre, Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing. Sci Transl Med 22 August 2012: Vol. 4, Issue 148, p. 148ra116 Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004129

Ricki Lewis About the Author: Ricki Lewis received her PhD in genetics from Indiana University. Her ninth book, The Forever Fix: Gene Therapy and the Boy Who Saved It, narrative nonfiction, was just published by St. Martin’s Press. Most of her other books are college life science textbooks, including "Human Genetics: Concepts and Applications," (10th edition, 2012) from McGraw-Hill Higher Education. Routledge Press published "Human Genetics: The Basics" in 2010. Ricki has published thousands of magazine articles, from Discover to Playgirl, but mostly in The Scientist. She is a genetic counselor at CareNet Medical Group in Schenectady, NY and teaches "Genethics" online for the Alden March Bioethics Institute of Albany Medical College. Ricki is a hospice volunteer and a frequent public speaker (Macmillan Speaker’s Bureau). Ricki’s blog Genetic Linkage is at www.rickilewis.com and she tweets at @rickilewis. Follow on Twitter @rickilewis.

The views expressed are those of the author and are not necessarily those of Scientific American.






Comments 2 Comments

Add Comment
  1. 1. naya8 3:47 am 08/23/2012

    If we ask ourselves why should ocasional mutation lead to a spesific and oriented change in the genume? we would find that the opposite is the true thing. that is;the phenotype which it who deals with the environment directely and not the gene, send its message to the genes to change according to that message. I thinke that the evolution works upon the phenotype and not ipon the genotype as it is known today.The main mechanism is accumolated changes and not natural selection.

    Link to this
  2. 2. Bill_Crofut 11:49 am 08/24/2012

    Dr. Lewis,

    The reference you provided is only available to me at unacceptable cost. However, you did provide a brief description of what seems to be one of the conclusions of the authors:

    “Some of the variants may have little or no effect, the consequence of a DNA replication error. It happens. But some may reflect the bacterium mutating towards yet another drug resistance. This is the essence of evolution: genetic change over time that affects the phenotype, thereby offering fodder for natural selection.”

    “May reflect” could very well be an attempt at caution on the part of the authors, but such reservation seems to have been supplanted by the assertion that drug resistance is evolutionary. It seems to me one could legitimately postulate the existence of drug resistance already present in the gene pool of the bacteria prior to exposure to the drug(s).

    Link to this

Add a Comment
You must sign in or register as a ScientificAmerican.com member to submit a comment.

More from Scientific American

Scientific American Holiday Sale

Black Friday/Cyber Monday Blow-Out Sale

Enter code:
HOLIDAY 2014
at checkout

Get 20% off now! >

X

Email this Article

X