Erin C. Gaynor, Ph.D. - 2002 Career Award in the Biomedical Sciences
2005 - Although many people have experienced the unwelcome effects of consuming certain bacteria along with their food, little is known about the intricacies of how the human digestive tract reacts to foodborne bacteria. We know that exposure to some species of bacteria in the gut can cause an immune response, and that the immune system can become tolerant to the presence of certain bacteria. But the precise interaction between bacteria and the human immune system is only beginning to be understood. Part of the reason for this is that many of the microbes in the gut do not grow well in a laboratory situation and many cannot be grown in a lab dish at all, says Erin Gaynor, a 2002 recipient of a BWF Career Award in the Biomedical Sciences and assistant professor of microbiology at the University of British Columbia.
Dr. Gaynor is interested in Campylobacter jejuni, the leading cause of bacterial foodborne illness in North America, producing an estimated 4 million illnesses per year. Most of these cases are the direct result of contact with raw or undercooked poultry or dairy products. Chickens and other poultry serve as natural hosts for the organism, which lives quite happily in the gut of healthy birds without causing illness. C. jejuni must also survive hostile environments such as refrigerators, kitchen counters, and cutting boards during transmission between unaffected (i.e., poultry) and susceptible (i.e., human) hosts. One focus of Dr. Gaynor’s research is on exploring the mechanisms C. jejuni uses to navigate this complicated transmission-infection cycle.
Like many infectious disease specialists, she has benefited from massive gene sequencing projects that have decoded the entire genomes of many infectious agents. The first complete sequence of a C. jejuni strain was published in 2000, and since then work has continued on sequencing several other infectious and noninfectious strains.
With the genomic data as a starting point, Dr. Gaynor set out to create a microarray, also known as a gene chip, that would enable her to simultaneously analyze the activity of thousands of genes at once. She wanted to use the array to compare how different varieties or strains of the bacteria react to different environmental and infection-related conditions by studying the level of activity of various genes. It took her a year to create and optimize the microarray tools that would enable her to do her first large-scale experiment. But she says that despite this time-consuming first step, having the microarray available has opened up many new avenues of research and led to some surprising results.
For instance, Dr. Gaynor recently discovered that C. jejuni uses the “stringent response,” a mechanism that enables bacteria to regulate their response to stresses such as changes in oxygen or moisture level, during both transmission and infection. The stringent response is typically used by bacteria that can enter host cells, a characteristic of particularly virulent strains of C. jejuni, and enables them to survive in harsh growth conditions. The discovery was the first description of the stringent response in any member of the C. jejuni family of bacteria, which includes a number of other organisms that cause human disease.
Additional research pointed to a key subset of genes that are regulated by the stringent response, including several that are related to the organism’s ability to infect humans.
To study the stringent response, Dr. Gaynor engineered a mutation, a change in the DNA sequence, of the survival enhancing spoT gene, that made it unable to invade human intestinal cells in laboratory experiments. The spoT gene encodes a bacterial protein that can produce a signal molecule, called an “alarmone,” which triggers the stringent response. Dr. Gaynor now is trying to understand whether this bacterial alarm system also plays a role in how susceptible human hosts respond to the presence of Campylobacter.
“We want to understand how changes in the bacteria that occur as a result of the alarmone tie in to disease and the host response,” she says. “In developing countries, people can develop a tolerance to Campylobacter, and we’d ultimately like to understand how cross-talk between the organism and humans contributes to disease severity.”
Understanding which C. jejuni genes are involved in the group of host-pathogen interactions that lead to foodborne illness rather than to placid coexistence could speed development of diagnostics to detect the organism in cases of foodborne outbreaks or track movement of drug-resistant variants. But in the meantime, the best ways to avoid Campylobacter are to keep meat preparation surfaces and tools clean to avoid contaminating uncooked items, such as salad, and to cook meat thoroughly, particularly during the upcoming summer barbeque months when incidence of Campylobacter infection tends to be highest.