Chlamydia trachomatis infection causes mitotic spindle pole defects independently from its effects on centrosome amplification

Traffic. 2011 Jul;12(7):854-66. doi: 10.1111/j.1600-0854.2011.01204.x. Epub 2011 May 12.

Abstract

Chlamydiae are Gram negative, obligate intracellular bacteria, and Chlamydia trachomatis is the etiologic agent of the most commonly reported sexually transmitted disease in the United States. Chlamydiae undergo a biphasic life cycle that takes place inside a parasitophorous vacuole termed an inclusion. Chlamydial infections have been epidemiologically linked to cervical cancer in patients previously infected by human papillomavirus (HPV). The inclusion associates very closely with host cell centrosomes, and this association is dependent upon the host motor protein dynein. We have previously reported that this interaction induces supernumerary centrosomes in infected cells, leading to multipolar mitotic spindles and inhibiting accurate chromosome segregation. Our findings demonstrate that chlamydial infection causes mitotic spindle defects independently of its effects on centrosome amplification. We show that chlamydial infection increases centrosome spread and inhibits the spindle assembly checkpoint delay to disrupt centrosome clustering. These data suggest that chlamydial infection exacerbates the consequences of centrosome amplification by inhibiting the cells' ability to suppress the effects of these defects on mitotic spindle organization. We hypothesize that these combined effects on mitotic spindle architecture identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism
  • Cell Cycle
  • Cell Cycle Proteins
  • Centrosome / metabolism*
  • Chlamydia Infections / complications
  • Chlamydia Infections / genetics*
  • Chlamydia Infections / metabolism*
  • Chlamydia trachomatis / pathogenicity*
  • Cyclin B1 / metabolism
  • Dyneins / metabolism
  • Female
  • HeLa Cells
  • Humans
  • Neoplasm Proteins / metabolism
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Securin
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / pathology*
  • Uterine Cervical Neoplasms / etiology
  • Uterine Cervical Neoplasms / virology

Substances

  • Antigens, Nuclear
  • Cell Cycle Proteins
  • Cyclin B1
  • NUMA1 protein, human
  • Neoplasm Proteins
  • Nuclear Matrix-Associated Proteins
  • Recombinant Fusion Proteins
  • Securin
  • Dyneins