Monday, 25 June 2018

Research Focuses on Tryptophan Starvation's Effect on Chlamydia

Tryptophan starvation appears to only partially disrupt the development of chlamydial development in high-risk human papillomavirus (HPV) negative C33A cell lines, according to research published in PLoS One.

“An HPV co-infection can render a chlamydial infection immunology silent, permitting that infection to recur after an interferon gamma-dependent post-immune response wanes,” Ashok Aiyar, PhD, associate professor of Microbiology, Immunology and Parasitology at the LSU School of Medicine, told Infectious Disease Advisor. Dr Aiyar was part of the research team that published the paper. “When you starve the cell of tryptophan, 1 of 2 things can happen: the bacterium can die completely or it can enter a quiescent state called persistence, where it's really not doing anything because it lacks the resources to replicate itself. And chlamydia can reactivate from persistence."

Interferon gamma is a protective cytokine against chlamydial infections because, as has been observed in epithelial cell-lines such as HeLa and HEp-2, it fosters the expression of an enzyme that helps disrupt production of the amino acid tryptophan. Tryptophan starvation limits the bacteria's ability to replicate.

Dr Aiyar said that his team discovered that tryptophan starvation did not completely block chlamydial development in cell-lines that were negative for high-risk HPV, such as C33A, while screening for cell-lines to identify those suitable for C trachomatis co-infections with other genital pathogens.

Working from the hypothesis that high-risk HPV oncogenes could modulate the effect of tryptophan starvation on chlamydial development, the researchers compared chlamydial development in HeLa and C33A cell-lines.

Dr Aiyar et al concluded that expression of the high-risk HPV E6 oncogene alone was sufficient to get C33A cells to behave like HeLa cells during tryptophan starvation. Tryptophan starvation prevents doxycycline from clearing C trachomatis out of HeLa cells but not C33A cells, allowing the dormant disease to reappear once the protective effect wears off.

Dr Aiyar said these results were in no way definitive, but they fit with long-time observations of the path of chlamydia.

“There is a rich history of chlamydia infections being ‘cleared,' then 6 months later or 1 year later, the patient presents with the exact same strain of chlamydia and with no indication they've been re-exposed,” he said. “It's an infection that went silent and recurred. The kind of scenario I'm painting could lead to that happening.”

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