"Bad" bacteria proves helpful - Antibiotics - Escherichia coli used in manufacturing erythromycin - Brief Article

The world is full of all kinds of bacteria--good, bad, and innocuous. Most often, it's the bad bacteria that catch our attention with their health-stealing antics. Yet, sometimes, as the old adage goes, it takes a thief to catch a thief. By hijacking the biosynthetic machinery of bacteria, scientists can create antibiotics to kill the bad bacteria that rob us of our vitality. Genetic engineers at Stanford (Calif.) University have inserted the largest working genes to date into the E. coil bacterium, transforming this run-of-the-mill microbe into an organism that can churn out new precursors of erythromycin, a broad-spectrum antibiotic and penicillin substitute, thus demonstrating a powerful tool for developing novel antibiotics to combat bacteria that have become resistant to overused ones.

Traditionally, manufacturers make erythromycin commercially through fermentation, using the soil bacterium Saccharopolyspora erythraea. The process is hard to scale up, creating a bottleneck in the drug-development process. S. erythraea grows slowly--a population of this bacterial strain takes four hours to double in number. A population of E. coli, in contrast, only takes 20 minutes to double. That, plus the fact that a great deal is already known about E. coli, used extensively in bioscience research, makes the latter the workhorse of choice in genetic engineering.

To modify erythromycin and give it novel properties, chemists start with a pure form and use chemistry to change the molecule--a costly approach. "If life is at stake, that expense is worthwhile," says Chaitan Khosla, professor of chemistry and chemical engineering. "In this experiment, instead of using chemistry, we program genes to make a modified erythromycin. It's a more efficient way to do genetic engineering than had ever been done before.

"Historically, bacteria have been great sources of new pharmaceuticals. Drugs have been isolated from all sorts of weird sources in nature and modified." In nature, bacteria may produce antibiotics to inhibit the growth of nearby strains that compete for nutritional resources.

The genetic engineers have "tweaked nature's strategies" to make antibiotics with novel properties. "The machinery is highly malleable and can be manipulated to make modified natural products," Khosla explains. Modifications may make antibiotics better able to combat resistant strains of bacteria.

COPYRIGHT 2002 Society for the Advancement of Education
COPYRIGHT 2002 Gale Group