A modified genome from one bacteria has been inserted into another.J. Craig Venter Institute.Posted on 08/22/2009 3:16:32 PM PDT by neverdem
Yeast cell surrogate may help scientists to engineer synthetic life.
A modified genome from one bacteria has been inserted into another.J. Craig Venter Institute.Scientists have devised a way to modify an organism that was previously impossible to genetically engineer in the lab.
The method, developed by researchers at the J. Craig Venter Institute in Rockville, Maryland, and San Diego, California, could aid the development of biomaterials and biofuels by helping scientists to genetically engineer species that have so far been beyond their reach. It could also aid the Venter institute's project to create synthetic life.
In their paper, published today in Science1, the researchers describe how they removed a genome from the bacterium Mycoplasma mycoides and transplanted it into the yeast Saccharomyces cerevisiae. They were then able to delete a gene from the M. mycoides genome — a feat that would not have been possible in the bacterium, because scientists lack the tools to genetically engineer the organism.
The team then inactivated an enzyme in a related bacterium, called Mycoplasma capricolum, that defends against invading organisms by destroying DNA that has not been tagged with certain chemical modifications, called methyl groups. The team also artificially added methyl tags to the M. mycoides genome to enable the bacterium to get past M. capricolum's defences.
The bioengineers then transplanted the modified M. mycoides genome into M. capricolum, where it was able to direct the M. capricolum cells to form colonies of M. mycoides.
"There are many synthetic-biology applications that need modification of bacteria on a large scale, and yet many organisms that are of interest in this space are not easy to manipulate genetically," says James Collins, a bioengineer at Boston University in Massachusetts, who was not involved with the research. "So this is really quite a nice advance from a genome engineering standpoint."
Last year, the Venter institute reported that it had synthesized the genome of a small bacterium, Mycoplasma genitalium, by stitching together fragments of it in yeast cells2. The institute has also transplanted the unmodified genome of M. mycoides into an M. capricolum bacterium3.
What researchers have not yet been able to do is transplant either a synthetic or native M. genitalium genome into Mycoplasma pneumoniae and 'boot up' the recipient bacteria with the new genetic code. That project has been hampered in part by the fact that M. genitalium grows very slowly, so it is difficult to explore the conditions that would allow a successful genome transplantation, the authors of the paper say. But the ability to manipulate the M. genitalium bacterium in yeast cells might also allow the team to remove any barriers that may stand in the way of a transplantation, the researchers say.
Overcoming these barriers are essential if bioengineers are to create synthetic life, says study author John Glass from the institute in Rockville. But Glass says that it is difficult to predict when that might happen. "It could be tomorrow, or it could be next year," he says. "We have yet to transplant a native M. genitalium into M. pneumoniae, and we're feverishly working on it, but we haven't got there yet."
Collins is confident that groups will soon be able to take that step, and that they will bill it as the first synthetic organism. "We'll probably see something like that in the next few months and groups will be pitching it as the first synthetic organism," he says. But Collins has stricter criteria for what constiutes synthetic life. "My sense of a synthetic organism is one you build from scratch — in that you're not basing the genome directly on an extant natural genome — and we're very far away from doing that," he says.
micro ping
Oh, organism.
Yeah, I read the same thing...
Just kidding (except about the "beer is life" part).
MYCOPLASMAS: SOPHISTICATED, REEMERGING, AND BURDENED BY THEIR NOTORIETY
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Authors: Joel B. Baseman, The University of Texas Health Science Center at San Antonio; and Joseph G. Tully, National Institute of Allergy and Infectious Diseases
No other group of procaryotes has been so embroiled in controversy and in establishing a clear pathogenic niche as the mycoplasmas. Their virulence determinants are undeniably complex, and their unique biological properties likely challenge the host differently from typical bacterial pathogens. Recently, mycoplasmas have been linked as a cofactor to AIDS pathogenesis and to malignant transformation, chromosomal aberrations, the Gulf War Syndrome, and other unexplained and complex illnesses, including chronic fatigue syndrome, Crohn's disease, and various arthritides. The earliest reports of mycoplasmas as infectious agents in humans appeared in the 1930s and 1940s.
Reports in the 1970s of M. fermentans in the joints of rheumatoid arthritis patients and in the bone marrow of children with leukemia raised expectations for its pathogenic potential; these findings have not been adequately confirmed. Sufficient evidence, however, has accumulated recently to establish an important and emerging role for M. fermentans in human respiratory and joint diseases. For example, M. fermentans has been detected by specific gene amplification techniques such as polymerase chain reaction (PCR) in the synovial fluid of patients with inflammatory arthritis, but not in the joints of patients with juvenile or reactive arthritis.
M. genitalium has been implicated as an etiologic agent in certain human joint diseases. This clinical correlation began with the observation of a mixed infection of M. pneumoniae and M. genitalium in synovial fluid specimens of a nonimmunocompromised patient after an acute respiratory infection. A predominant role was not established for either Mycoplasma species in the initial respiratory disease or in the joint manifestations, although evidence to implicate postinfectious autoimmunity to both organisms was described. These findings prompted a PCR assay on synovial fluids from patients with various arthritic syndromes, which presented case reports on two of 13 patients with M. genitalium detected in joint fluids.
While patients with antibody defects or those receiving immunosuppressive drugs appear to be the most susceptible to infections with mycoplasmas present in healthy tissues, emerging evidence indicates that contact with other mycoplasmas in the environment is an important hazard. For example, the direct isolation of a feline mycoplasma (M. felis) from the joint of a hypogammaglobulinemic patient with septic arthritis was recently reported, with suspected transmission occurring through a cat bite 6 months before the onset of arthritis. Other examples include fatal septicemia caused by M. arginini, a common animal mycoplasma, from blood and multiple tissue sites in a slaughter house employee who had advanced non-Hodgkin's lymphoma and hypogammaglobulinemia, and a septicemic infection with a canine mycoplasma (M. edwardii) in a patient with advanced AIDS (M.K.York, pers. comm.).
One of the most critical aspects of mycoplasmal infections in immunodeficient patients is the frequent inability to control such infections with appropriate broad spectrum antibiotics. Although the tetracyclines and erythromycins are effective chemotherapeutic agents for many mycoplasmal infections, M. fermentans and M. hominis strains are usually resistant to erythromycin, and tetracycline-resistant strains of M. hominis and U.urealyticum have been reported from the lower urogenital tract of patients. However, these antibiotics and most other broad spectrum agents have limited mycoplasmacidal activity in vivo, and their efficacy eventually depends on an intact host immune system to eliminate the mycoplasmas. Most hypogammaglobulinemic patients lack the ability to mount a strong antibody response. Guidelines for managing such mycoplasmal infections in patients with immune defects should include immediate in vitro testing of the isolated mollicute against a wide range of antibiotics; expeditious administration of the antibiotic by the most appropriate route (intravenously, if warranted); prolonged therapy terminated only if there is no rapid clinical or microbiological response; and possibly administration of intravenous immunoglobulin.
Molecular mimicry is especially interesting since it has been suggested for decades that mycoplasmas provoke an antiself response that triggers immune disorders, although the basis for the induction has been elusive. A classic example of bacteria-mediated autoimmune disorders is the development of acute rheumatic fever following streptococcal infection.
The Latest Controversies: Food for Thought or the Twilight Zone
Gulf War Syndrome
One of the most controversial current medical issues is whether the multiple acute and chronic symptoms found in veterans of the Persian Gulf War were caused by chemical exposure, infectious agents, or psychological problems, or whether a Gulf War Syndrome exists at all. The clinical illness comprises a collection of symptoms, including chronic fatigue, joint pain, headaches, and skin rashes. One study suggests that pathogenic mycoplasmas are responsible for a large number of cases among veterans, on the basis of DNA hybridization and the responsiveness of veterans to prolonged antibiotic treatment. Even though the experimental evidence is sparse and incomplete and well-controlled and detailed studies by independent laboratories are needed, if the Gulf War Syndrome has infectious causes, mycoplasmas with their requisite biological credentials are potential candidates.
Egad! Jurassic Mildew!
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