Infection and immunity, July 2018, Vol.86(7)
Some members of the genus , including the human pathogen , infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to GI tropism. Infectivity and shedding of wild-type (WT) and three mutants containing nonsense mutations in different cytotoxin genes, , , and , were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in , was highly attenuated for GI infection and had a GI 50% infectious dose (ID) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.
Chlamydia ; Gastrointestinal Infection ; Genital Tract Immunity ; Intracellular Bacteria ; Intracellular Pathogen ; Sexually Transmitted Diseases ; Tropism ; Chlamydia Infections -- Etiology ; Chlamydia Muridarum -- Pathogenicity ; Chromosomes -- Physiology ; Gastrointestinal Diseases -- Etiology ; Reproductive Tract Infections -- Etiology
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