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Chlamydia overcomes multiple gastrointestinal barriers to achieve long-lasting colonization

2021; Elsevier BV; Volume: 29; Issue: 11 Linguagem: Inglês

10.1016/j.tim.2021.03.011

1878-4380

Guangming Zhong,

Urinary Tract Infections Management

Chlamydia mutants deficient in plasmid-encoded factors are more defective in colonizing the upper gastrointestinal (GI) tract while those deficient in chromosome-encoded factors are more defective in colonizing the lower GI tract. Chlamydia may have acquired the plasmid for promoting its spread to the large intestine while using the chromosomal genes for maintaining its long-lasting colonization in the large intestine. The plasmid-encoded pGP3 is critical for Chlamydia to resist both gastric acid in the stomach and CD4+ T lymphocyte-mediated immunity in the small intestine, and it may play similar roles in aiding chlamydial infection in the female genital tract. The chromosomal proteins TC0237 and TC0668 are essential for chlamydial evasion of innate lymphoid cell (ILC)3-secreted interferon (IFN)γ in the large intestine and they may also enable Chlamydia to evade innate IFNγ in the genital tract. The Chlamydia muridarum (CM)–mouse gut interactions may represent a productive platform for both discovering novel mechanisms of microbe–host interactions and revealing pathogenic mechanisms of Chlamydia in the genital tract. CM colonization in the gut is long-lasting and nonpathogenic, which may be useful for both modeling microbiota–gut interactions and exploring the medical significance and utility of gastrointestinal Chlamydia. 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. 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.