• Tiny jumping genes fingered as culprit i

    From ScienceDaily@1:317/3 to All on Tuesday, April 05, 2022 22:30:38
    Tiny jumping genes fingered as culprit in rise of antibiotic resistance
    Activity levels of transposons provide the handle needed for selection to spread antibiotic resistance from wild microbes to human pathogens

    Date:
    April 5, 2022
    Source:
    Duke University
    Summary:
    Biomedical engineers believe they have discovered the physical
    mechanism that causes high doses of antibiotics to promote the
    spread of antibiotic resistance between bacteria. The culprit, they
    say, is an overabundance of 'jumping genes,' called transposons,
    that carry the genetic instructions for resistance from the cell's
    source code to plasmids that shuttle between cells.



    FULL STORY ========================================================================== Biomedical engineers at Duke University believe they have discovered the physical mechanism that causes high doses of antibiotics to promote the
    spread of antibiotic resistance between bacteria.


    ==========================================================================
    The culprit, they say, is an overabundance of "jumping genes," called transposons, that carry the genetic instructions for resistance from
    the cell's source code to plasmids that shuttle between cells.

    The results appeared online March 28 in the journalNature Ecology &
    Evolution.

    "There's a lot of evidence that suggests human pathogens likely pick
    up antibiotic resistance from other species living in the natural
    environment," said Lingchong You, professor of biomedical engineering
    at Duke. "Intuitively, it makes sense that high levels of antibiotics
    in these environments are facilitating the jumping of resistance genes
    from chromosomes to plasmids so that they can spread, but the underlying mechanism never been directly tested.

    That's where our work comes in." It's no secret that the rise in
    antibiotic resistance in human pathogens has coincided with the rise in
    the use of antibiotics in large-scale industrial endeavors like farming
    and manufacturing. While the genes that provide resistance appear to be relatively new to these pathogens, some date back millions of years in
    bacteria living in certain wild ecosystems. Coupled with experiments that
    show high levels of antibiotics promote the spread of resistance both
    within and between bacterial species, it's easy to draw the conclusion
    that human pathogens have acquired these resistance genes from the
    environment due to its increasing ambient levels of antibiotics.

    While the cause and effect seems clear, research has never firmly
    established the underlying mechanisms, You said. Scientists know that
    small, free-floating bundles of DNA called plasmids carry resistance
    genes between cells. You's own research, however, has shown that the
    presence of antibiotics does not increase the rate at which plasmids
    carry out these gene swaps. What then, the researchers asked, is the fundamental force driving this natural selection?


    ==========================================================================
    In the new paper, You and his postdoc Yi Yao show that this mysterious mechanism could be the antibiotic-mediated selection on "jumping genes,"
    called transposons, that carry the resistance genes from the cell's
    chromosomes to the plasmids.

    "Yi's experiments were designed to test this possible pathway
    that explains how different pathogens actually get resistance from environmental species," You said. "And he demonstrated that not only
    is this possible, it's also very likely." Transposons are tiny pieces
    of DNA that constantly jump around the inside of a cell. They can jump
    from place to place within a cell's central genetic database, and they
    can jump from the database of the DNA to the larger plasmids capable of traveling between cells, or vice versa. This can lead to chromosomes or plasmids that contain many copies of the same genetic blueprints.

    In a series of experiments, Yao exposed cells resistant to various types
    of antibiotics to a range of concentrations of that antibiotic. As the concentration increased, invariably there came a point at which the
    cells carrying plasmids with more copies of the resistance genes began outcompeting their peers.

    "All the curves looked almost exactly the same," You said. "It's actually surprising just how robust the trend is." The researchers say that the
    copy number of transposons on the plasmids affects how many antibiotic resistance proteins the cell is producing. That production comes at
    an energy cost, and it's not until the amount of antibiotics reaches a
    certain level that the extra energy expended is a valuable trait to carry.



    ==========================================================================
    It is not clear, however, if the higher levels of antibiotics are
    directly causing the resistance transposons within these cells to become
    more active.

    Rather, it demonstrates that if the transposon jumping is already
    happening, antibiotic selection would always enrich the population
    containing resistance genes that have jumped to plasmids.

    The levels of antibiotics required to begin driving this selection, the researchers say, varies greatly between species and the specific drugs in question. But this range is not uncommon in today's natural environments, potentially providing the pressure needed for human pathogens to pick
    up the resistance genes with more regularity.

    "We're now working to prove that this dynamic is actively occurring
    in real environments like hospitals and not just in a Petri dish," You
    said. "We also want to see if we can use this knowledge to selectively
    dial in the flow of genes to optimize bacteria engineered for industrial
    uses." This work was supported by the National Institutes of Health (R01A1125604, R01GM110494, R01EB029466), the National Science Foundation (MCB-1937259) and the David and Lucile Packard Foundation.


    ========================================================================== Story Source: Materials provided by Duke_University. Original written
    by Ken Kingery. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Yi Yao, Rohan Maddamsetti, Andrea Weiss, Yuanchi Ha, Teng Wang,
    Shangying
    Wang, Lingchong You. Intra- and interpopulation transposition of
    mobile genetic elements driven by antibiotic selection. Nature
    Ecology & Evolution, 2022; DOI: 10.1038/s41559-022-01705-2 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220405102828.htm

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