Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors

Infect Immun. 2018 Jun 21;86(7):e00141-18. doi: 10.1128/IAI.00141-18. Print 2018 Jul.

Abstract

Some members of the genus Chlamydia, including the human pathogen Chlamydia trachomatis, 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 Chlamydia muridarum plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to C. muridarum GI tropism. Infectivity and shedding of wild-type (WT) C. muridarum and three mutants containing nonsense mutations in different cytotoxin genes, tc0437, tc0438, and tc0439, were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in tc0439, was highly attenuated for GI infection and had a GI 50% infectious dose (ID50) 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 tc0439 mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in tc0600 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.

Keywords: Chlamydia; gastrointestinal infection; genital tract immunity; intracellular bacteria; intracellular pathogen; sexually transmitted diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chlamydia Infections / etiology*
  • Chlamydia Infections / immunology
  • Chlamydia muridarum / pathogenicity*
  • Chromosomes / physiology*
  • Codon, Nonsense
  • Cytotoxins / genetics
  • Female
  • Gastrointestinal Diseases / etiology*
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Tract / microbiology
  • Genitalia / microbiology
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • Polymorphism, Single Nucleotide
  • Reproductive Tract Infections / etiology*
  • Reproductive Tract Infections / immunology
  • Tropism*

Substances

  • Codon, Nonsense
  • Cytotoxins