Figure 2

Chlamydia/host tryptophan cycle. Solid arrows indicate conversion by the enzyme in green on the arrow; dotted arrows show movement across membranes. Induction of increased levels of tryptophan dioxygenase by IFN-γ causes flux of the host pool of tryptophan into the kynurenine pathway, causing starvation of Chlamydia parasites for tryptophan. Starvation for tryptophan presumably derepresses the trpR-regulated operon of tryptophan biosynthesis (trpBDCEbEa kynU kprS) in C. psittaci. The host-pathway enzymes of interest are located in the cytosol or are located in the mitochondrial compartment. Genes of tryptophan biosynthesis are named in the order of the pathway steps, following the nomenclature used by Xie et al. [30]. Thus, trpAa and trpAb (absent in C. psittaci) encode the large (aminase) and small (glutamine-binding) subunits of anthranilate synthase, trpB encodes anthranilate phosphoribosyl transferase, trpC encodes phosphoribosyl-anthranilate isomerase, trpD encodes indoleglycerol phosphate synthase, and trpEa and trpEb encode the α and β subunits of tryptophan synthase, respectively. KynU encodes kynureninase. kprS (synonymous with prsA) encodes PRPP synthase. Orange arrows indicate induction of indoleamine 2,3-dioxygenase and nitric oxide synthase by IFN-γ. Blue lines indicate inhibition of the latter two enzymes by nitric oxide and 3-hydroxyanthranilate, respectively.