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Increased sensitivity to tryptophan bioavailability is a positive adaptation by the human strains of C hlamydia pneumoniae
Author(s) -
Chacko Anu,
Barker Christopher J.,
Beagley Kenneth W.,
Hodson Mark P.,
Plan Manuel R.,
Timms Peter,
Huston Wilhelmina M.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12701
Subject(s) - biology , microbiology and biotechnology , interferon , tryptophan , indoleamine 2,3 dioxygenase , interferon gamma , intracellular , infectious dose , strain (injury) , virology , chlamydophila pneumoniae , in vitro , chlamydia , immunology , chlamydiales , amino acid , virus , genetics , anatomy
Summary One of the most significant activities induced by interferon‐gamma against intracellular pathogens is the induction of IDO (indoleamine 2,3‐dioxygenase) expression, which subsequently results in the depletion of tryptophan. We tested the hypothesis that human strains of C hlamydia pneumoniae are more sensitive to tryptophan limitation than animal C . pneumoniae strains. The human strains were significantly more sensitive to IFN ‐γ than the animal strains in a lung epithelia cell model ( BEAS ‐2 B ), with exposure to 1 U ml −1 IFN ‐γ resulting in complete loss of infectious yield of human strains, compared to the animal strains where reductions in infectious progeny were around 3.5–4.0 log. Strikingly, the IFN ‐γ induced loss of ability to form infectious progeny production was completely rescued by removal of the IFN ‐γ and addition of exogenous tryptophan for the human strains, but not the animal strains. In fact, a human heart strain was more capable of entering a non‐infectious, viable persistent stage when exposed to IFN ‐γ and was also more effectively rescued, compared to a human respiratory strain. Exquisite susceptibility to IFN ‐γ, specifically due to tryptophan availability appears to be a core adaptation of the human C . pneumoniae strains, which may reflect the chronic nature of their infections in this host.