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Preventing STDs: A Step in the Right Direction
CHORI Scientists Develop New Therapeutic Approach Against Chlamydia trachomatis

April 9, 2012 – Chlamydia trachomatis is an intracellular parasite that is the number one global bacterial cause of sexually transmitted disease (STD), resulting in over 100 million cases each year according to the World Health Organization. C. trachomatis infection causes pelvic inflammatory disease and infertility, and enhances the acquisition and transmission of human immunodeficiency virus (HIV). There are currently no vaccines or microbicides that can protect against C. trachomatis infection. CHORI Senior Scientist Deborah Dean, MD, MPH, and her colleagues, however, have just developed a novel, phage-based therapeutic that is effective against C. trachomatis and may provide a model for targeting other bacteria that cause STDs as well.

“We now have a therapeutic construct that is effective against C. trachomatis, and our goal is to incorporate it into a microbicide formulation. The efficacy is excellent in vitro, and we are making additional improvements to ultimately prevent C. trachomatis infection all together,” says Dr. Dean.

 

“We now have a therapeutic construct that is effective against C. trachomatis, and our goal is to incorporate it into a microbicide formulation. The efficacy is excellent in vitro.”



In the study, published early online in Biomaterials, Dr. Dean and her colleagues detail how they genetically engineered a phage that would effect the ability of C. trachomatis to reproduce.

"Phages are small particles amenable to genetic manipulation. There are many different kinds, and they are basically able to enter cells and sometimes insert their own genomic sequences into bacteria," explains Dr. Dean. "In this study, we had to genetically add two elements to the phage. One was DNA encoding a short peptide that would target the host cell, and the other was DNA encoding a short piece of a protein taken from C. trachomatis that we hoped would effect how the organism would grow in host cells."

The results of the study demonstrate for the first time that an engineered phage approach could be the key to developing a successful microbicide against C. trachomatis infection. In particular, Dr. Dean and her colleagues showed that the engineered phage did in fact enter the host cell, and entered the vacuole in which the organism replicates, resulting in knockdown of the organism without any adverse effects on the cell.

“Our findings are just what you want to see. When you create something artificial that you are adding to cells, you hope it will target the infection you want to eliminate and not the host cells. That’s exactly what we saw here.”

While the phage wasn’t 100 percent effective in eliminating the ability of the C. trachomatis to replicate, it demonstrated a significant impact.

“When you think about a vaccine or a microbicide, even one that is only 50 percent effective would be well accepted given the option of no intervention,” says Dr. Dean. “Although the knockdown wasn’t complete, it’s a great step in the right direction.”

While additional studies are needed to understand how the phage is interfering with C. trachomatis replication, ultimately the results of Dr. Dean’s study show that a phage-based approach is a viable option for ultimately preventing C. trachomatis transmission and infection, and may potentially provide a model for other bacteria that cause STDs as well.

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Sunday, July 29, 2012 12:44 PM

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