Abstract
Chlamydia trachomatis (CT) is frequently detected in the human gastrointestinal (GI) tract despite its leading role in sexually transmitted bacterial infections in the genital tract. Chlamydia muridarum (CM), a model pathogen for investigating CT pathogenesis in the genital tract, can also colonize the mouse GI tract for long periods. Genital-tract mutants of CM no longer colonize the GI tract. The mutants lacking plasmid functions are more defective in colonizing the upper GI tract while certain chromosomal gene-deficient mutants are more defective in the lower GI tract, suggesting that Chlamydia may use the plasmid for promoting its spread to the large intestine while using the chromosome-encoded factors for maintaining its colonization in the large intestine. The plasmid-encoded Pgp3 is critical for Chlamydia to resist the acid barrier in the stomach and to overcome a CD4(+) T cell barrier in the small intestine. On reaching the large intestine, Pgp3 is no longer required. Instead, the chromosome-encoded open reading frames TC0237/TC0668 become essential for Chlamydia to evade the group 3-like innate lymphoid cell-secreted interferon (IFN)γ in the large intestine. These findings are important for exploring the medical significance of chlamydial colonization in the gut and for understanding the mechanisms of chlamydial pathogenicity in the genital tract.