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Arsenic Eating Bacteria Discovered!!!

What Poison? Bacterium Uses Arsenic to Build DNA and Other Molecules

From elephants to the bacterium Escherichia coli, all forms of life on Earth depend on the same six elements: oxygen, carbon, hydrogen, nitrogen, phosphorus, and sulfur. “The paradigm is that the chemistry of life is so specific that any change in chemistry also changes molecular stability and reactivity, which would not be tolerated,” says Clara Chan, a geomicrobiologist at the University of Delaware, Newark.

In a paper published online by Science ( this week, however, an exception to that rule makes a surprising debut. Meet GFAJ-1, a bacterial strain that researchers say can replace the phosphorus in its key biomolecules, including DNA, with the legendary poison arsenic. “This is a very impressive and exciting discovery,” says Barry Rosen, a biochemist at Florida International University in Miami. “The implication of this work is that life can be quite different from what we know,” agrees Chan.
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    Search for unusual life. 
    Felisa Wolfe-Simon collects samples from Mono Lake (left), where high arsenic levels proved conducive to the evolution of arsenic-using microbes.
    In 2009, Felisa Wolfe-Simon, a geomicrobiologist based at the U.S. Geological Survey in Menlo Park, California, and two colleagues argued that arsenic could have stood in for phosphorus in ancient living systems. Phosphorus, in the form of the compound phosphate, forms the backbone of strands of DNA and RNA, as well as ATP and NAD, two molecules key to energy transfer in a cell. Arsenic, Wolfe-Simon pointed out, sits just below phosphorus on the periodic table and has similar chemical properties. Indeed, its toxicity to people and most forms of life arises when cells try to use arsenic in lieu of phosphorus.
    Despite that, Wolfe-Simon speculated that some microbes might be able to adapt to using arsenic. Others were skeptical. The arsenic-containing compound arsenate is much more unstable than phosphate in water, and no cell would be able to cope with that, critics argued.
    To test her hypothesis, Wolfe-Simon collected mud from Mono Lake, California, a desert body of water known for having high arsenic levels, and grew the microorganisms from it in increasing concentrations of arsenate. She didn't add any phosphate or other phosphorus-containing compounds to the growth medium, as is typically done to sustain microbes. Instead, she periodically transferred the growing cultures to a new dish to reduce the concentration of any original phosphorus to the point that any microbe making new DNA or other biomolecules would need to use the arsenic to survive.

    Like others, says Wolfe-Simon, she didn't really expect to find any survivors. So she was thrilled and surprised when one evening she checked the latest cultures under the microscope and saw fast-moving bacteria. She rechecked the components of the culture media to confirm there were no phosphorus contaminants. She and her colleagues then began to subject the microbes to sophisticated analyses to see if arsenic had been utilized by the bacteria. “I held my breath with every one,” says Wolfe-Simon.
    One form of mass spectrometry showed that the arsenic was inside the bacterial cells and not some impurity sticking to the outside of the cell. When the researchers added radioactively labeled arsenate to the bacteria's culture, they were later able to discern its presence in the protein, lipid, nucleic acid, and metabolite fractions of the cells, suggesting that arsenic had been incorporated in molecules forming each fraction. They also separated out the DNA from the bacteria and analyzed its composition using a technique called high-resolution secondary ion mass spectrometry; the isolated DNA contained arsenic.
    Tests utilizing the intense x-rays at a synchrotron facility offered additional support, indicating that at least some of the arsenic in the bacteria was in the form of arsenate with the appropriate molecular bonds to carbon and oxygen atoms to replace the phosphates in DNA and other molecules.
    Such work has convinced many that Wolfe-Simon's team has isolated a bacterium that uses arsenic to grow. “The organization of the experiments presents convincing and exhaustive results,” says Milva Pepi, an environmental microbiologist at the University of Siena in Italy. But not everyone agrees. Rosen finds the study “believable” but says he still has lingering concerns that the arsenic is simply concentrated in the bacterial cell's extensive vacuoles and not incorporated into its biochemistry. He would like to see Wolfe-Simon's team demonstrate a functional arsenic-containing enzyme, for example. Steven Benner, an astrobiologist at the Foundation for Applied Molecular Evolution in Gainesville, Florida, is more skeptical: That GFAJ-1 uses arsenic as a replacement for phosphorus, “is, in my opinion, not established by this work,” he says.
    Wolfe-Simon isn't arguing that GFAJ-1 prefers, or even naturally uses, arsenic. Mono Lake has a lot of phosphorus as well as arsenic, and the strain grows better when supplied with phosphorus. But to her and others, GFAJ-1 is proof that phosphorus-free life forms can exist and may do so somewhere on Earth. Next, Wolfe-Simon wants to collect samples from places with high arsenic but low phosphorus concentrations in hopes of finding microbes that depend solely on the former.
    Wolfe-Simon speculates that organisms like GFAJ-1 could have thrived in the arsenic-laden hydrothermal vent–like environments of early Earth, where some researchers think life first arose, and that later organisms may have adapted to using phosphorus. Others say they'll refrain from such speculation until they see more evidence of GFAJ-1's taste for arsenic and understand how the DNA and other biomolecules can still function with the element incorporated. “As in this type of game changer, some people will rightly want more proof,” says microbiologist Robert Gunsalus of the University of California, Los Angeles. “There is much to do in order to firmly put this microbe on the biological map.”

    Concerns Aired About Arsenic-Containing Bacteria

    A debate that erupted 5 months ago over whether a bacterium incorporates arsenic into its DNA is about to start simmering again. Today online in Science eight research groups voice their concerns about a paper thatappeared 2 December 2010 online in Science and will be published in next week's issue of the journal. The original article presented an exception to one of the fundamental rules of life on Earth. To survive, microbes, plants, and animals all require six essential elements: oxygen, carbon, nitrogen, hydrogen, sulfur, and phosphorus. But NASA astrobiology fellow Felicia Wolfe-Simon and her colleagues isolated a bacterium that, when grown with high arsenic concentrations and no added phosphorus, appears to replace some phosphorus with the chemically similar arsenic in key biomolecules, including DNA.
    A startling discovery in and of itself, the finding became even more controversial because a NASA press announcement in December implied a connection to the search for extraterrestrial life. Yet many scientists were sharply critical of the paper, including several who blogged about their concerns in posts that drew hundreds of comments that offered additional attacks on the work. When journalists tried to follow up, Wolfe-Simon, then at the U.S. Geological Survey in Menlo Park, California, and her colleagues initially declined to respond, fuelingspeculations about the soundness of the research. The group eventually posted a response. And in a subsequent interview, Wolfe-Simon said she and her co-authors welcomed the debate but, "We wanted to be able to have that discourse in the scientific community, as a record."
    That discourse has now begun with the so-called Technical Comments published today online by Science, along with a response by Wolfe-Simon and her colleagues. The exchange does not put forth new data on the matter, but centers on the original experiments in which Wolfe-Simon isolated bacteria from arsenic-laden Mono Lake, California, and then tried to grow them in cultures with large amounts of arsenic and no phosphorus, which is typically required for growth. One strain called GFAJ-1 still managed to multiply, despite the dearth of phosphorus, the original paper reported
    Several of the Technical Comments question whether contamination or background levels of phosphorus in the cultures could have fueled this growth. Another researcher worries that the DNA that was described as likely having arsenic incorporated in its structure might have been contaminated. Others suggest that arsenic compounds are too unstable to replace phosphorus compounds and be functional. "Their hypothesis that this microorganism contains DNA and other standard biomolecules in which arsenate atoms replace phosphorus atoms would, if true, set aside nearly a century of chemical data concerning arsenate and phosphate molecules," writes Steven Benner, an astrobiologist at the Foundation for Applied Molecular Evolution in Gainesville, Florida, in one of the Technical Comments
    Wolfe-Simon's team has acknowledged that there were indeed trace amounts of phosphorus in the media used, contributed by mineral salts—they even noted this in their paper. But Wolfe-Simons maintains there was not enough background phosphorus to drive the bacterial growth.
    University of British Columbia microbiologist Rosie Redfield, the blogger most critical of Wolfe-Simon both personally and professionally, asserts in one of the Technical Comments that Wolfe-Simon did not go far enough in purifying DNA from GFAJ-1 before testing it for its arsenic components.
    The issue of whether arsenic-containing molecules would be stable in a cell is the subject of three of the Technical Comments. In the cytoplasm, arsenate would be reduced to arsenite, which would not be able to substitute for phosphate, Barbara Schoepp-Cothenet, from the Bioénergétique et Ingénierie des Protéines in Marseilles, France, and colleagues, claim in one comment. Moreover, phosphates are incorporated into DNA early in a multistep process, and an arsenic substitute would be unlikely to survive that process intact, notes Benner.
    In a response accompanying the Technical Comments, Wolfe-Simon and her co-authors point to work by others that suggests that these arsenic compounds would last longer when part of large biomolecules. Her group has proposed that the bacterium might sequester the arsenic compounds to protect them from breaking down. "In the comments, there were lots of good points that were raised," says Wolfe-Simon's co-author Samuel Webb, a biogeochemist at the Stanford Synchrotron Radiation Lightsource in Menlo Park, California. "With anything this intriguing or controversial, there will always be multiple sides."
    Examples of "lowly bacteria found in a foul-smelling hot spring near Mono Lake, California is a living window into Earth’s early history, a time when photosynthesis was barely evolved and the atmosphere non-existent." 
    In a note published along with the comments and the response, Bruce Alberts, Science's Editor-in-Chief, acknowledges that the debate over the bacterium is far from over, writing: "We recognize that some issues remain unresolved. However, the discussion published online today is only a step in a much longer process."

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