EXECUTIVE SUMMARY

New research has identified a potential target for drug treatment of chlamydia, which may help develop alternate approaches to stem infections.

  • Chlamydia is the most commonly reported sexually transmitted infection in the U.S. More than 1.7 million cases were diagnosed in 2017, with 45% of diagnoses among females ages 15-24 years.
  • The Aptima Combo 2 Assay and the Xpert CT/NG are the first lab tests that have been approved for extragenital diagnostic testing of Chlamydia trachomatis and Neisseria gonorrhoeae infections via the throat and rectum; previously, these tests were only cleared for testing urine, vaginal, and endocervical samples.

Reproductive health providers battle against chlamydia every day, as it is the most commonly reported sexually transmitted infection (STI) in the U.S. According to data from the CDC, more than 1.7 million cases were diagnosed in 2017, with 45% among females ages 15-24 years.1 New research has identified a potential target for drug treatment that may help develop alternate approaches to stem infections.2

Tryptophan is essential to Chlamydia trachomatis (CT) bacteria for survival; the bacteria looks to its host cells for the necessary amino acid. To avoid tryptophan starvation, genital CT strains conditionally create a enzyme known as tryptophan synthase, allowing CT strains to use a molecule known as indole to make tryptophan.

Ocular CT create an inactive version of tryptophan synthase or have lost the gene for the enzyme entirely, according to scientists. Researchers at the Louisiana State University (LSU) Health Sciences Center in New Orleans set out to determine why ocular strains of CT no longer make an active tryptophan synthase.

Ashok Aiyar, PhD, associate professor of microbiology, immunology and parasitology at LSU Health New Orleans School of Medicine, says the investigative team’s work demonstrates that small molecules known as trp operon de-repressors, which are produced by the gut microbiome and carried by the circulation to other parts of the body, are key to the process. These molecules force CT to make tryptophan synthase; however, activation of tryptophan synthase in the absence of indole generates ammonia, which rapidly kills CT.2

“As such, our findings provide new leads for therapeutics against chlamydia infections that leverage products made by the gut microbiome,” states Aiyar.

Previous research indicates that trp de-repressors fight such pathogenic bacteria as Legionella pneumophila and Mycobacterium tuberculosis via unknown mechanisms. The mechanism described for CT may extend to these bacteria as well, says Aiyar. The LSU investigative team plans to research mechanisms to restrict the availability of indole in cells in the genital area, which should annihilate CT strains.

FDA Clears New Tests

In May 2019, the FDA approved two new tests that can detect CT and Neisseria gonorrhoeae through diagnostic testing of extragenital specimens. The Aptima Combo 2 Assay and the Xpert CT/NG are the first tests approved for extragenital diagnostic testing of these infections via the throat and rectum. Previously, these tests were only cleared for testing urine, vaginal, and endocervical samples.

“It is best for patients if both of these sexually transmitted infections are caught and treated right away, as significant complications can occur if left untreated,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in a statement. “[These] clearances provide a mechanism for more easily diagnosing these infections.” (Read the FDA statement online at: https://bit.ly/2Wk4LtE.)

Approval for the tests was based on study results performed by the Antibacterial Resistance Leadership Group, a research consortium funded by the National Institute of Allergy and Infectious Diseases. The study was designed to determine how well the two tests detected these infections in extragenital samples.3 Investigators used a master protocol study design, allowing tests of multiple diagnostics from different manufacturers on each sample.

The study enrolled nearly 2,600 adults seeking STI testing at nine clinics across the United States. Both symptomatic and asymptomatic participants enrolled in the trial. Clinicians collected pharynx and rectal swabs from consenting participants, with investigators testing the samples with each diagnostic. Study results indicate the two tests accurately identified extragenital chlamydia and gonorrhea infections.3

Development of the master protocol trial design may have a broad effect on diagnostic development, according to researchers. By testing several products using samples from the same patient, efficiency is increased and clinical study costs are reduced. By streamlining the process, development of new and improved diagnostics may be expedited not only for STIs, but also other infectious diseases such as pneumonia, urinary tract infections, and bloodstream infections.

REFERENCES

  1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017. Atlanta: U.S. Department of Health and Human Services; 2018.
  2. Sherchand SP, Aiyar A. Ammonia generation by tryptophan synthase drives a key genetic difference between genital and ocular Chlamydia trachomatis isolates. Proc Natl Acad Sci USA 2019;116:12,468-12,477.
  3. Doernberg S. Performance of nucleic acid amplification tests for the detection of Neisseria Gonorrhoeae and Chlamydia trachomatis in extragenital sites. Presented at 2019 ASM Microbe; San Francisco, June 2019.