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Forward Genetic Approaches in Chlamydia trachomatis
09:03

Forward Genetic Approaches in Chlamydia trachomatis

Published on: October 23, 2013

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Inter-species lateral gene transfer focused on the Chlamydia plasticity zone identifies loci associated with

Zoe E Dimond1, Robert J Suchland2, Srishti Baid1

  • 1Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.

Molecular Microbiology
|November 5, 2021
PubMed

Insights

Chlamydia muridarum and Chlamydia trachomatis show different host adaptations. Genetic analysis revealed that factors beyond the plasticity zone, including an inclusion protein, are critical for chlamydial pathogenesis and host specificity.

Area of Science:

  • Microbiology
  • Genetics
  • Pathogenesis

Background:

  • Chlamydia muridarum infects mice effectively, modeling human genital tract disease, while Chlamydia trachomatis infections are limited in mice.
  • Understanding the genetic basis for these host specificity differences is crucial but challenging due to genomic similarity.

Purpose of the Study:

  • To investigate the role of the plasticity zone (PZ) in Chlamydia host adaptation and specificity.
  • To identify specific genes responsible for differential tropism and cytopathic effects between C. muridarum and C. trachomatis.

Main Methods:

  • Generation of hetero-genomic Chlamydia strains via lateral gene transfer, replacing C. trachomatis PZ regions with those from C. muridarum.
  • In vitro and in vivo analyses of chimeric strains to assess growth, infection capabilities, and cytopathic effects.

Main Results:

  • Chimeric strains exhibited C. trachomatis-like growth but poor mouse infection, suggesting PZ is not solely responsible for mouse tropism.
  • Cytotoxicity was not attributed to the three large putative cytotoxins (LCTs) in the C. muridarum PZ.
  • A novel inclusion protein (CTL0402/CT147 and TC0424 homolog) was identified as essential for inclusion integrity and preventing apoptosis.

Conclusions:

  • The plasticity zone is not the sole determinant of differential host tropism between C. muridarum and C. trachomatis in mice.
  • Chlamydial cytotoxicity and cytopathic effects are mediated by factors other than the previously suspected LCTs.
  • The identified inclusion protein plays a critical role in chlamydial pathogenesis by maintaining inclusion stability and evading host cell death.
Keywords:
chlamydiacytopathic effectplasticity zone

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