Tryptophan recycling is responsible for the interferon‐γ resistance of Chlamydia psittaci GPIC in indoleamine dioxygenase‐expressing host cells

• Published in: Molecular microbiology Vol. 52; no. 3; pp. 903 - 916
• Main Authors: Wood, Heidi, Roshick, Christine, McClarty, Grant
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2004; Blackwell Science; Blackwell Publishing Ltd
• Subjects: Amino Acid Sequence; Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Chlamydia psittaci; Chlamydophila psittaci - genetics; Chlamydophila psittaci - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; HeLa Cells; Humans; Interferon-gamma - metabolism; Microbiology; Miscellaneous; Molecular Sequence Data; Operon; Sequence Alignment; Tryptophan - metabolism; Tryptophan Oxygenase - genetics; Tryptophan Oxygenase - metabolism; Resistance; Chlamydiaceae; Microbiology; Aminoacid; Cytokine; Chlamydiales; Chlamydia psittaci; Tryptophan; Bacteria; Recycling; Gamma interferon
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2004.04029.x

Summary Comparative genomics indicates that vast differences in Chlamydia sp. host range and disease characteristics can be traced back to subtle variations in gene content within a region of the chromosome termed the plasticity zone. Genes required for tryptophan biosynthesis are located in the plasticity zone; however, the complement of genes encoded varies depending on the chlamydial species examined. Of the sequenced chlamydia genomes, Chlamydia psittaci GPIC contains the most complete tryptophan biosynthesis operon, encoding trpRDCFBA. Immediately downstream of the trp operon are genes encoding kynureninase and ribose phosphate pyrophosphokinase. Here, we show that, in GPIC, these genes are transcribed as a single transcript, the expression of which is regulated by tryptophan. Complementation analyses, using various mutant Escherichia coli isolates, indicate that the tryptophan biosynthesis, kynureninase and ribose phosphate pyrophosphokinase gene products are functional. Furthermore, growth of C. psittaci GPIC in HeLa cells, cultured in tryptophan‐free medium, could be rescued by the addition of anthranilate, kynurenine or indole. In total, our results indicate that this complement of genes enables GPIC to recycle tryptophan and thus accounts for the interferon‐γ resistant phenotype displayed in indoleamine‐2,3‐dioxygenase‐expressing host cells.