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Catching the Culprits
CHORI Scientist Garners Highly Prestigious NIH FIRCA to Genotype Chlamydia Trachomatis Strains in Ecuador

"In particular, we're looking at genotypes related to persistence, and whether we can identify any host genetic markers that may make people more susceptible to infection and disease."

Deborah Dean, MD, MPH, a CHORI scientist for the Center for Immunobiology and Vaccine Development, has just received a Fogarty International Research Collaboration Award (FIRCA) from the NIH in order to study the pathogenesis of various strains of Chlamydia trachomatis (CT) in Ecuador. Designed to foster collaborative research with scientists in developing countries, FIRCAs are both coveted and highly competitive.

“FIRCAs are quite hard to get,” acknowledges Dr. Dean. “You need to have an established track record in a developing country with academic colleagues in addition to a track record of NIH R01 funding. Besides all of that, the competition is very keen. It’s terribly exciting to have been selected.”

With over 20 years of research in developing countries under her belt, Dr. Dean was an ideal candidate for a FIRCA, not only because of her established work in developing nations but also because of the importance of CT research in particular.

“Sexually transmitted diseases, or STDs, caused by Chlamydia are a global epidemic,” says Dr. Dean. “CT is the leading cause of STDs in both the developed world and the third world.”

The overall goal of the grant is to create genotype profiles, or fingerprints, as Dr. Dean calls them, for each different Chlamydia strain that can then be correlated with host genetic immune profiles and clinical findings.

In addition to traditional genotyping methods, Dr. Dean will be using a multi-locus sequence typing (MLST) scheme that her lab has developed for CT. A decade-old concept that has been successfully used for typing other human pathogens, MLST will be used to type CT strains for the first time in Dr. Dean’s study.

“The traditional gold standard is to take one gene and sequence it to arrive at a genotype,” explains Dr. Dean. “With MLST, the concept is that in addition to the gold standard, you also take several housekeeping genes – genes which are not under immune selection and rarely change but are essential for the organism to stay alive – and you sequence them. Then all of the genes become part of your fingerprinting scheme instead of just one gene.”

In the short term, this kind of fingerprinting of CT strains is a tremendously powerful research tool which can be used to precisely identify which strains are the culprits for which phenotypic profiles. Does one strain cause more inflammation than another? Does another strain result in greater susceptibility to disease?
"You can use it on a global scale to compare with other strains in different countries, to determine how strains move geographically, and to identify how they evolve. You can track treatment efficacy and virulence."
"It provides a whole host of information that you wouldn't normally have," explains Dr. Dean, "which tells you not only how different strains behave and what their impact is, but how best to treat the strains as well."

In addition to helping identify best treatment practices, this invaluable information will be used to answer a number of unresolved questions about CT, such as whether recurrent infections actually represent persistence instead of re-infection, and whether persistence is associated with unique host genetic profiles. Yet the longer term implications of Dr. Dean's research are even more important.

As Dr. Dean often points out, no disease in the world has ever been cured with the use of antibiotics, the only treatment option currently available for STDs caused by CT.

"Being able to precisely identify different strains and their impact on the human host will eventually allow us to develop a vaccine that's going to have maximum global impact," says Dr. Dean. "That, of course, is always the ultimate goal."


Tuesday, May 17, 2011 8:19 AM

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