The Biologist and the Bacteria
It's rare to see the words“Escherichia coli—commonly shortened to E. coli—not followed by the word “outbreak” in news headlines. But to Associate Professor of Biology Iruka Okeke, the bacteria often associated with diarrheaâ€”and deathâ€”are the victim of some bad press.
“Most E. coli strains are harmless. They help with digestion, and some even protect us from harmful organisms,” says Okeke, the recent recipient of a more than $500,000 National Science Foundation (NSF) grant to study the microbe.“The bacteria you hear about on the news are like the headlines about Afghanistan. Most Afghans are peaceful people, but you mostly hear news about the terrorists.”
The grant, the second round of NSF funding that Okeke has received, will support more than half of her students' summer research projects and thesis research. And it may, if past research is any indication, shed new light on the two sides of the maligned bacterium that outnumbers our own cells.
Earlier in her career, Okeke had unearthed an old scientific paper that discussed proteins on the surface of bacteria. She had long been intrigued by research on the ability of E. coli to colonize the gut, cause diarrhea, and then survive it. Even on a good day, the intestines are subject to flash flooding. "My thought was that they must be exceptional hangers-on, or they would get washed out,” she says.“I hypothesized that this surface protein could be one of the proteins that helped certain E. coli to hang on, and it was."
Okeke and her students have studied this and related proteins, with NSF support, since her arrival at Haverford. That blend of research and teaching is what drew Okeke to Haverford after a brief stint at the University of Bradford in Yorkshire, in her native England, following her graduation from Obafemi Awolowo University in Ife, Nigeria, and postdoc work at the University of Maryland.“I really wanted to work at a place where I could do research and teach and where both things were taken very seriously,” she says. "When I came to Haverford for the interview, I loved it. It was exactly what I was imagining in my head "the ability to teach students biology through research" and I canceled all my other interviews. Thank God I got the job!” she says with a laugh.
Using research as a teaching tool has some unusual payoffs. In 2003, one of Okeke's students, Adaobi Nwaneshiudu '03, made a discovery that changed the thinking on one category of diarrhea causing E. coli. “She overturned what seemed like a very small thing that was pretty much considered 'known' in my field,” says Okeke.“She proved we were all wrong.”
Until Nwaneshiudu saw something on one of her gels that no one else seemed to see, science believed enteropathogenic E. coli carried one plasmid, a circular, self-replicating DNA molecule, different from chromosomal DNA, that only holds a few genes. Enteropathogenic E. coli's plasmid was encoded for adherence, or "hanging on," as Okeke puts it, allowing the microbe to colonize the inhospitable walls of intestines.
What her student discovered was that E. coli has a second plasmid—this one for antibiotic resistance. The bacterium not only readily shares this antibiotic resistance plasmid with its own kind, it's able to pass it to other, unrelated, microbes which then become armored against current antibiotics.
Antibiotic resistance is a global problem, and is critical in developing countries like Nigeria, where Okeke's parents were born and where they sent their four children to secondary school. “In Nigeria, they're using old antibiotics because newer ones are simply not affordable until the patent expires,” explains Okeke, who has taken some of her students to Nigeria and Ghana to study resistance firsthand.
“Because of that, they're using drugs that bacteria have already become resistant to.” (Okeke explores some of those issues in depth in her book Divining Without Seeds: The Case for Strengthening Laboratory Medicine in Africa, published in 2011 by Cornell University Press.)
In 2007, Okeke and Nwaneshiudu co-wrote a paper on this second plasmid, which was published in The Journal of Bacteriology and has since been cited in other studies on antimicrobial-drug resistance.
Nwaneshiudu, who was born in Nigeria, is now a Ph.D. and M.D. finishing her residency in the dermatology department at the University of Chicago. She credits Okeke with inspiring her to keep one foot in the lab while the other is in the treatment room.“Iruka has been a good role model, I have to say,” says Nwaneshiudu.“It's because of her gentle enthusiasm for her field that I decided to get a dual degree that would allow me to see patients and still be involved at some level with research endeavors. I hope to make a contribution one dayâ€”Iruka helped keep that fire going.”
And she's been a role model in another way, for the ever-vexing work-life balance of a scientist, says Nwaneshiudu.“She now has a cute little baby!” Okeke and her husband, a policy analyst, who runs an Africa-based think-tank, have an infant daughter, Chika.
Okeke's latest grant will take her research and her student-scientists one step furtherâ€”to a deeper understanding of E. coli's remarkable adherence abilities and its relationship to other genes and proteins that could lead to ways to“intervene” to treat and prevent diarrheal diseases, one of the leading causes of death among African children. (The U.S. isn't spared, either. One category of E. coli, referred to as 0157:H7, causes about 73,000 illnesses and 50 to 60 deaths every year, according to the Centers for Disease Control and Prevention.)
Okeke doesn't expect to have all the answers when her latest grant expires in 2016. She says her family always asks,“When are you going to finish your research?”
“I say never,” she says, smiling,“because one question opens up all new ones, many of them coming from the students themselves. But it's good, because it's constantly energizing and I'm never, ever bored!”
Denise Foley is contributing executive editor for Prevention magazine and has been a health journalist for almost 30 years.