Distinct Roles of Chromosome- versus Plasmid-Encoded Genital Tract Virulence Factors in PromotingChlamydia muridarumColonization in the Gastrointestinal Tract

ABSTRACTThe genital pathogenChlamydiais known to colonize the gastrointestinal tract. Orally deliveredChlamydia muridarumcan reach the colon and maintain a long-lasting colonization there. However,C. muridarumwith mutations in chromosomal genestc0237andtc0668(designated a chromosomal mutant) or deficient in plasmid-encoded pGP3 (designated a plasmid mutant) is unable to do so. We now report that the chromosomal mutant is still able to reach the colon while the plasmid mutant fails to do so following an oral delivery, suggesting that lack of colon colonization by different mutants may involve distinct mechanisms. Consistently, a direct intracolonic delivery selectively restored the ability of the plasmid mutant, but not the chromosomal mutant, to colonize the colon. The chromosomal mutant was rescued only in the colon of mice deficient in gamma interferon (IFN-γ). Thus, the chromosomal mutant’s deficiency in colonizing colonic mucosal tissue is likely due to its increased susceptibility to IFN-γ-mediated immunity. Furthermore, IFN-γ deficiency was sufficient for rescuing colon colonization of an orally delivered chromosomal mutant but not plasmid mutant while mice deficient in gastric acid production rescued the plasmid mutant but not the chromosomal mutant. Both mutants are attenuated in inducing genital tract pathology. Thus, we propose that chlamydial chromosomal-gene-encoded genital tract virulence factors may be essential forChlamydiato maintain long-lasting colonization in the colon while the plasmid may enableChlamydiato reach the colon by promoting evasion of gastric barriers.