Genetic differences in the Chlamydia trachomatis tryptophan synthase alpha-subunit can explain variations in serovar pathogenesis

The human pathogen Chlamydia trachomatis is an obligate intracellular bacte rium, characterized by a developmental cycle that alternates between the in fectious, extracellular elementary bodies and intracellular, metabolically active reticulate bodies, The cellular immune effector interferon gamma (IF N-gamma) inhibits chlamydial multiplication in human epithelial cells by in duction of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase. IFN -gamma causes persistent C, trachomatis serovar A infections with atypical reticulate bodies that are unable to redifferentiate into elementary bodies and show diminished expression of important immunogens, but not of GroEL. However, the sensitivity to IFN-gamma varies among serovars of C, trachomat is. In our previous study significant IFN-gamma-specific, but tryptophan re versible, induction of proteins in C. trachomatis A and L2 with molecular m asses of approximately 30 and 40 kDa was observed on 2D-gels, The 30-kDa pr otein from C. trachomatis L2 migrated with a significantly lower molecular weight in C, trachomatis A. In this paper we include C. trachomatis B, C an d D in our investigations and identify the proteins as alpha- and beta-subu nits of the chlamydial tryptophan synthase using matrix-assisted laser deso rption/ionization mass spectrometry. DNA sequencing of the trpA genes from C, trachomatis A and C shows that thr TrpA in these serovars is a 7.7-kDa t runcated version of C. trachomatis D and L2 TrpA. The truncation probably i mpairs the TrpA activity, thus elucidating a possible molecular mechanism b ehind variations in the pathogenesis of C, trachomatis serovars. (C) 2000 E ditions scientifiques et medicales Elsevier SAS.