When it comes to human health, few bacterial organisms have a reputation as nasty as E. coli’s. The term is practically synonymous with foodborne illness. But a UB engineer’s research project shows that there’s a flip side to this story—that this reviled little organism could actually save human lives.
For more than a decade, Blaine Pfeifer, UB associate professor of chemical and biological engineering, has been studying how to transform E. coli into tiny factories for producing new forms of antibiotics. His work centers on erythromycin, a drug used to treat a wide range of infections, from pneumonia to syphilis.
Like other antibiotics, erythromycin is a naturally occurring compound. In nature, it’s produced by a bacterium called Saccharopolyspora erythraea, which grows relatively slowly and responds poorly to genetic engineering. These traits mean that scientists can use S. erythraea to make erythromycin, but not easily experiment with generating new versions of the antibiotic.
That’s where E. coli comes in: The microbe grows quickly and accepts new genes readily. In addition, most strains, including those used in Pfeifer’s lab, pose no danger to humans.
“We simply view E. coli as a great engineering platform through which we can produce and modify important compounds like antibiotics with an expanded set of biological tools,” Pfeifer says.
This spring, he announced a major milestone in his research: In the journal Science Advances, he and his lab reported that they had created strains of E. coli that successfully produced never-before-seen varieties of erythromycin. His team included UB graduate students Yi Li and Lei Fang, and postdoctoral associate Guojian Zhang, who was first author on the paper.
Pfeifer’s research effort, spanning many years, involved two broad steps: First, he and his colleagues altered the organism’s DNA so that it generated all the chemical building blocks needed to construct erythromycin molecules—a process analogous to stocking a car factory with all the parts necessary for building a vehicle. With that done, the scientists turned to tweaking the assembly line, that is, engineering E. coli’s genetics further so that the bacteria produced a form of erythromycin with a slightly different structure from the version hospitals use today.
Three of the new varieties of erythromycin killed bacteria recalcitrant to other antibiotics—an important finding in a world where doctors and hospitals are struggling to treat “superbugs,” bacterial infections that have developed a resistance to existing drugs.
“We look at this as one contribution to the emerging theme of solutions to the antibiotic-resistance crisis,” Pfeifer says. “As opposed to searching for completely new antibiotic compounds, our approach leverages the engineering capabilities of the E. coli platform to significantly alter the chemical diversity of an established antibiotic.
“Our system allows us to engage in a game of molecular chess between mechanisms bacteria use to thwart antibiotics and the engineering capabilities we have to produce new compounds.”
Pfeifer notes that despite its notoriety, E. coli is actually a “workhorse” in the biotechnology sector, a product of its flexibility in accepting new genes.
Early bioengineering applications of E. coli included using the organism to synthesize insulin, which was previously obtained from pigs. More recently, Pfeifer says, E. coli has been engineered to produce biofuels and other “commodity” chemicals in high global demand.
“E. coli’s ubiquitous use in these industries is often completely ignored compared to the contamination scares, which arise from pathogenic strains that no one works with in the biotech world,” Pfeifer says. “It’s unfortunate that these beneficial applications aren’t equally recognized.”
The next step in his own E. coli research is to continue modifying the species to improve the antibacterial qualities of the erythromycin it makes. The ultimate goal is to generate a drug effective enough to use in hospitals when other antibiotics fail. If that happens, we’ll have E. coli to thank.