LSU Health Research Finds New RX Target for Common STD

Article

Research led by Ashok Aiyar, PhD, associate professor of microbiology, immunology and parasitology at LSU Health New Orleans School of Medicine, has identified a target that may lead to the development of new treatments for the most common sexually transmitted infection in the U.S. The results are published this month online in PNAS, available here.

Chlamydia is caused by infection with Chlamydia trachomatis bacteria. It can affect both the urogenital tract and the eyes. If untreated, the outcome of both ocular and genital infections can be severe. Ocular Chlamydia infections are the leading cause of infectious blindness, and genital infections can lead to infertility. The health of infants born vaginally to infected mothers is also often severely compromised.

Chlamydia trachomatis bacteria need the essential amino acid, tryptophan, to survive. They are dependent upon their host cells, or the microbiome, to provide it. Genital Chlamydia strains have a unique mechanism to avoid tryptophan starvation. By conditionally making an enzyme called tryptophan synthase, they can use a molecule called indole, which is sometimes made by the genital microbiome, to make tryptophan. Ocular strains make an inactive version of tryptophan synthase or have lost the gene for the enzyme entirely. The goal of this research was to discover why ocular Chlamydia no longer make an active tryptophan synthase.

Aiyar says, "Our studies demonstrate that small molecules, collectively called trp operon de-repressors, which are produced by the gut microbiome and carried by the circulation to other parts of the body, play a key role. These molecules force Chlamydia to make tryptophan synthase. However, activation of tryptophan synthase in the absence of indole generates ammonia, which kills Chlamydia very rapidly. As such, our findings provide new leads for therapeutics against chlamydia infections that leverage products made by the gut microbiome."

Previous studies have shown that trp de-repressors also kill other pathogenic bacteria, such as Legionella pneumophila and Mycobacterium tuberculosis, via unknown mechanisms.

"It is possible that the mechanism we have described for Chlamydia extends to these other bacteria as well," notes Aiyar.

According to the Centers for Disease Control and Prevention (CDC), Louisiana had one of the highest rates of reported cases of Chlamydia trachomatis in the United States in 2017. The CDC reported there were more than 1.7 million cases of chlamydia diagnosed in 2017, representing a 22% increase from 2013 levels. However, the CDC estimates that 2.86 million infections occur annually. A large number of cases are not reported because most people with chlamydia are asymptomatic and do not seek testing.

Next steps include research on the mechanisms to restrict the availability of indole in cells in the genital area, thereby creating conditions under which trp de-repressors will effectively kill genital Chlamydia by forcing the production of ammonia.

The research team also included Dr. Shardulendra Sherchand, a fellow in the Department of Microbiology, Immunology and Parasitology at LSU Health New Orleans School of Medicine.

The research was supported by a grant from the National Institutes of Health.

Source: LSU Health Sciences Center New Orleans 

Related Videos
Set of white bottles with cleaning liquids on the white background. (Adobe Stock 6338071172112 by zolnierek)
Medical investigators going over data. (AdobeStock 589197902 by Wasan)
CDC logo is seen on a laptop. (Adobe Stock 428450603 by monticellllo)
Association for the Health Care Environment (Logo used with permission)
COVID-19 germs, fungi, bacteria objects. (Adobe Stock 584704860 by chawalit)
Ambassador Deborah Birx, , speaks with Infection Control Today about masks in schools and the newest variant.
mRNA technology  (Adobe Stock 485886181 by kaptn)
Ambassador Deborah Birx, MD
Woman lying in hospital bed (Adobe Stock, unknown)
Related Content