Multinucleation During C. Trachomatis Infections Is Caused by the Contribution of Two Effector Pathways

PLoS One. 2014 Jun 23;9(6):e100763. doi: 10.1371/journal.pone.0100763. eCollection 2014.


Chlamydia trachomatis is an obligate intracellular bacterial pathogen and the second leading cause of sexually transmitted infections in the US. Infections cause significant morbidity and can lead to serious reproductive sequelae, including an epidemiological link to increased rates of reproductive cancers. One of the overt changes that infected cells exhibit is the development of genomic instability leading to multinucleation. Here we demonstrate that the induction of multinucleation is not conserved equally across chlamydial species; C. trachomatis L2 caused high levels of multinucleation, C. muridarum intermediate levels, and C. caviae had very modest effects on multinucleation. Our data show that at least two effector pathways together cause genomic instability during infection leading to multinucleation. We find that the highly conserved chlamydial protease CPAF is a key effector for one of these pathways. CPAF secretion is required for the loss of centrosome duplication regulation as well as inducing early mitotic exit. The second effector pathway involves the induction of centrosome position errors. This function is not conserved in three chlamydial species tested. Together these two pathways contribute to the induction of high levels of genomic instability and multinucleation seen in C. trachomatis infections.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Centrosome
  • Chlamydia Infections / microbiology*
  • Chlamydia Infections / pathology*
  • Chlamydia trachomatis / physiology*
  • Chromosome Segregation
  • DNA, Bacterial / metabolism
  • Endopeptidases / metabolism
  • Fluorescent Antibody Technique
  • Giant Cells / microbiology*
  • Giant Cells / pathology*
  • Griseofulvin / pharmacology
  • HeLa Cells
  • Humans
  • Mice
  • Mitotic Index
  • Models, Biological
  • Mutation
  • Signal Transduction*
  • Species Specificity
  • Spindle Apparatus / metabolism


  • DNA, Bacterial
  • Griseofulvin
  • Endopeptidases
  • CPA factor