Engineered E coli to fight antibiotic-resistant bacteria

Researchers have successfully engineered E coli bacteria to produce new forms of antibiotics - including three that show promise in fighting drug-resistant bacteria.
Blaine A Pfeifer, an associate professor of chemical and biological engineering in the University at Buffalo School of Engineering and Applied Sciences, has been studying how to engineer Escherichia coli (E coli) to generate new varieties of erythromycin, a popular antibiotic.
In the new study, Pfeifer and colleagues report that they have done this successfully, harnessing E coli to synthesise dozens of new forms of the drug that have a slightly different structure from existing versions.
Three of these new varieties of erythromycin successfully killed bacteria of the species Bacillus subtilis that were resistant to the original form of erythromycin used clinically.

"We're focused on trying to come up with new antibiotics that can overcome antibiotic resistance, and we see this as an important step forward," said Pfeifer.
"We have not only created new analogs of erythromycin, but also developed a platform for using E coli to produce the drug," he said.

Over the past 11 years, Pfeifer's research has focused on manipulating E coli so that the organism produces all of the materials necessary for creating erythromycin.
With that phase of the research complete, Pfeifer has turned to the next goal: Tweaking the way his engineered E coli produce erythromycin so that the drug they make is slightly different than versions used in hospitals today.

The process of creating erythromycin begins with three basic building blocks called metabolic precursors - chemical compounds that are combined and manipulated through an assembly line-like process to form the final product, erythromycin.
To build new varieties of erythromycin with a slightly different shape, scientists can theoretically target any part of this assembly line, using various techniques to affix parts with structures that deviate slightly from the originals.
In the new study, Pfeifer's team focused on a step in the building process that had previously received little attention from researchers, a step near the end.
The researchers focused on using enzymes to attach 16 different shapes of sugar molecules to a molecule called 6-deoxyerythronolide B.

Every one of these sugar molecules was successfully adhered, leading, at the end of the assembly line, to more than 40 new analogs of erythromycin - three of which showed an ability to fight erythromycin-resistant bacteria in lab experiments.
"The system we've created is surprisingly flexible, and that's one of the great things about it," Pfeifer said.
"We have established a platform for using E coli to produce erythromycin, and now that we've got it, we can start altering it in new ways," he said.
The research was published in the journal Science Advances.