½ñÈÕ³Ô¹Ï

Element of Surprise

½ñÈÕ³Ô¹Ï biologists investigate a gut-wrenching mystery.

Deep in the basement of the biology building, Anand Panchal ’13 spent the last semester infecting human cells with one of the most devastating microbes on earth. 

The bacterium in question is enteropathogenic Escherichia coli (known as EPEC), a sinister pathogen that is one of the developing world’s leading causes of diarrhea—a disease that is easily managed with modern medicine, but which can be deadly to children in impoverished regions with limited access to quality health care. Diarrhea is the second-highest cause of death among children under five years old, according to the World Health Organization, killing 1.5 million of them in the year 2009 alone.

For the past three years, Professor Jay Mellies [biology 1999–] and his students have been investigating an unconventional weapon in the battle against EPEC—zinc.

EPEC attaches to the cells of the intestine, and assaults them with corrosive proteins. This makes it difficult or impossible for the gut to absorb nutrients; instead of digesting food and discarding the waste as excrement, the body rejects it wholesale and flushes it down the alimentary canal, resulting in dehydration, malnourishment, and even death.

But new findings suggest that there may be a way to mitigate EPEC’s devastating effects. Epidemiological studies in developing countries show that patients who receive zinc, a metal commonly used to prevent corrosion of other metals by rust, recover faster and suffer fewer symptoms.

Exactly how zinc subdues EPEC remains unclear, however—which is where ½ñÈÕ³Ô¹Ï comes in. Professor Mellies, who specializes in the genetics of bacteria, first began investigating the question at the behest of researchers at the University of Buffalo and the University of New Mexico, who suspected that zinc was specifically altering the bacterium’s gene expression to make it less virulent.

Mellies found no evidence for that theory, but he did discover something else. Somehow zinc disrupts the membrane around each cell of EPEC that allows it to destroy the lining of the intestine. In the same way that zinc protects chain-link fences from corrosion by rain and salt, it protects gut cells from corrosion by bacteria. “It’s not necessarily killing the bacteria, it’s just knocking them down a little,” explains Mellies, who published these results together with his colleagues last year in BMC Microbiology.

Though they now have a better idea of what is happening, Mellies and Panchal are continuing to unravel exactly how zinc weakens the EPEC membrane. One possibility is that zinc makes it harder for EPEC to latch onto the intestinal lining; another is that it makes it harder for it to release the proteins that actually corrode the lining.

Mellies has worked with several ½ñÈÕ³Ô¹Ï students in this line of inquiry, including Katherine Thomas ’11, Michael Turvey ’12, and Neil Evans ’12, who are listed as coauthors on the BMC Microbiology paper. The project, which is funded by the National Institutes of Health, is not just giving a token role to students. “Our research is student driven,” says Mellies. “It’s student dependent. I couldn’t have done the work without them.”

“It’s been a bumpy ride with some successes and some failures, but I have enjoyed the lab work immensely,” says Panchal, who plans to attend either medical school or a PhD program in microbiology, and is glad for the chance to work on a project with “immediate healthcare implications.”

Armed with a better understanding of how zinc eases the symptoms of EPEC and other forms of E. coli diarrhea, health authorities are more likely to adopt it as a standard therapy. Indeed, with antibiotic resistance becoming more pervasive, the need for alternative treatment is more intense than ever. Nor is the issue confined to developing nations. In 2011, an outbreak of foodborne E. coli disease in Germany resulted in 51 deaths and thousands of cases of serious illness. “Acute diarrheal infections are a huge problem worldwide,” says Mellies, who is optimistic that zinc can play an important role in treating the disease.

Political science major Alex Blum ’14 is a lover, a fighter, and a Quest editor. He’s mostly just a Quest editor, though.

Tags: Research, Professors, Students, Health/Wellness