Primer on Microbial Genomics cont'd
A Historic Microbe: The bacterium Clostridium acetobutylicum enjoys an unusual place in history. This microbe was discovered in 1915 by Chaim Weizmann, who noted its ability to convert starch into the organic solvents acetone and butanol, which have multiple applications in industrial settings. Shortly afterward, Great Britain used C. acetobutylicum to generate acetone for producing cordite for artillery shells in World War I. In gratitude for Weizmann's work, the British government offered to honor him, but he asked instead for support of a Jewish homeland in Palestine. This led to the Balfour Declaration of 1917, committing Britain to sanction what became in 1948 the state of Israel, with Weizmann as its first president.
Scientists hope the availability of this bacterium's genomic sequence, finished in 1999, will lead to a better understanding of its biochemistry and eventually to the replacement of current processes that rely on petroleum and natural gas for organic solvent production. Additionally, some Clostridia species are major pathogens. One produces the food toxin that causes botulism, and others are responsible for such rapidly spreading infections as tetanus and gangrene. DNA sequence comparisons of these species could yield insights into what enables some to cause harm to humans.
Superbug Survives Radiation, Eats Toxic Waste: A can of spoiled meat and nuclear waste may appear to have little in common, but the bacterium Deinococcus radiodurans thrives in both environments. This bacterium was discovered in 1956 when it was identified as the culprit in a can of spoiled ground beef thought to be radiation ”sterilized.” Scientists subsequently learned that its extreme radiation resistance enables the microbe to survive doses thousands of times higher than would kill most organisms, including humans. The remarkable DNA-repair processes of D. radiodurans allow it to stitch together flawlessly its own radiation-shattered genome in about 24 hours.
DOE chose this organism for DNA sequencing because of its potential usefulness in cleaning up waste sites containing radiation and toxic chemicals. Its DNA sequence was completely determined in 1999, and scientists now are exploring ways to add genes from other organisms to expand D. radiodurans’ capabilities for removing toxic wastes from contaminated sites. The added genes encode proteins that transform heavy metals to a more benign biomass and allow the concentration of heavy metals and the breakdown of organic solvents such as toluene. Studies into this organism’s remarkable DNA-repair pathways also may help scientists better understand how defects in human cellular processes might lead to the development of cancers.
Electron photomicrograph of D. radiodurans (sequenced in the DOE Microbial Genome Program), typically found as a cluster of four cells (a tetrad). D. radiodurans and related species have been identified worldwide, including in Antarctic granite and in water-shielding tanks of powerful 60Cobalt irradiators in Denmark. [Image and graph data by the Deinococcus team (Uniformed Services University of the Health Sciences]
The radiation-resistance profile of D. radiodurans compared to such other organisms as the common intestinal bacterium Escherichia coli, cockroaches, and humans. When older colonies of D. radiodurans are used, their survival extends much farther, to around 17kGy (1.7 million rads). Scientists believe this extreme radiation resistance may be a side effect of D. radiodurans' ability to survive severe dehydration, which also fragments DNA. [Nature Biotechnology 18, 85-90 (January 2000)] [Image and graph data by the Deinococcus team (Uniformed Services University of the Health Sciences]
Deinococcus radiodurans: The Ultimate Assembly Machine
The upper panel depicts DNA fragments extracted from D. radiodurans cells after high doss of radiation. The lower panel shows an intact, repaired DNA molecule hours later. Both panels depict "optical maps" of molecules viewed on a slide through an optical light microscope. Understanding the remarkable DNA-repair mechanisms of D. radiodurans may offer insights into some human cancers caused by DNA damage. [photos provided by David Schwartz (University of Wisconsin, Madison)]
D. radiodurans 1.75 million rads, 0 h
D. radiodurans 1.75 million rads, 24 h
[photos provided by David Schwartz (University of Wisconsin, Madison)]
Ordered restriction map (colored circle) and optical of a single circular 415,000-base (415-kb) DNA molecule snipped apart using a special DNA-cutting protein, the restriction enzyme Nhe I. Circular DNA elements are difficult to identify using nonoptical approaches, since these molecules break and become linear elements. Optical mapping generates a picture of the entire genome's architecture, revealing the number of chromosomes and the existence of extrachromosomal elements. This technique was critical to the discovery that D. radiodurans has four chromosomal elements rather than just one.
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Text from Human Genome Program, U.S. Department of Energy, Microbial Genome Program Report, 2000.
