Embargoed by Nature until 1 p.m. CST Wednesday, Feb. 2
Contacts:
David H. Sherman, Ph.D., (612) 626-0199
Teri Charest, Academic Health Center Communications, (612) 624-4604
U OF MINNESOTA SCIENTISTS FIND KEY TO NEW ANTIBIOTICS IN SOIL BACTERIUM
MINNEAPOLIS / ST. PAUL--University of Minnesota scientists have resolved a 50-year mystery regarding the creation of powerful antibiotics by common soil bacteria. The finding will be published in the Feb. 3 issue of Nature.
Soil bacteria produce some of the most important pharmaceuticals--including erythromycin, streptomycin and tetracycline--that have provided cures for such deadly diseases as tuberculosis, strep throat and infections by so-called "flesh-eating bacteria." More recently, powerful new drugs from common soil microbes have lowered cholesterol levels in millions of people and have prolonged the lives of individuals with organ transplants and cancer.
Microbiologists Yongquan (Alex) Xue, a graduate student, and David Sherman, an associate professor, have dissected the biochemical machinery by which the soil bacterium Streptomyces venezuelae generates biologically active molecules known as macrolides. Biologically active molecules are ones with the ability to kill--as in the case of macrolides--or disable the functioning of cells of a different species. This work allowed them to decipher how the various parts of the machine work individually and how they fit together to make a functioning biosynthetic system.
"With this understanding we can hope to create large numbers of new structures with such useful biological activities as antibiotic, antifungal, anticancer or immunosuppressive activity," said Sherman, who is also director of the university's Microbiology, Immunology and Molecular Pathobiology graduate program and a faculty member in the university's department of microbiology and Biological Process Technology Institute.
S. venezuelae and its compounds were first isolated about 50 years ago by scientists in New York, who determined that instead of producing a single biologically active compound, the bacterium had the unusual capability of generating four different compounds. It has generally been assumed since that discovery that the bacterium makes the macrolides through a linear and highly constrained biochemical process.
Xue and Sherman have now demonstrated that S. venezuelae's assembly line actually branches in at least two different directions, with the capability of producing multiple biologically active compounds. The versatility of the assembly line has led scientists to propose new ways in which bacteria can generate important new pharmaceuticals. More importantly, by having multiple compounds in its arsenal, the bacterium can confound the ability of invading bacteria to develop counterdefenses. This ability may someday be harnessed to fight the ever-increasing threat of drug resistant bacteria.
While scientists do not know for sure why bacteria, fungi and plants make compounds that have biological activity, they are quite certain that bacteria use them as a defense mechanism against a sea of potential predator microbes. The chemicals may also serve in a signalling or communication role.
In 1998 Sherman and his colleagues established the basic architecture of the biochemical machinery, including the number of proteins and the order and identity of the genes on the chromosome, and proved the function of the system. That work was published in the Proceedings of the National Academy of Sciences.
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