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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