Chlamydia Induces Anchorage Independence in 3T3 Cells and Detrimental Cytological Defects in an Infection Model

Abstract

Chlamydia are Gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. Chlamydia trachomatis is the causative agent of the sexually transmitted infection (STI) Chlamydia, the most commonly acquired bacterial STI in the United States. Chlamydial infections have also been epidemiologically linked to cervical cancer in women co-infected with the human papillomavirus (HPV). We have previously shown chlamydial infection results in centrosome amplification and multipolar spindle formation leading to chromosomal instability. Many studies indicate that centrosome abnormalities, spindle defects, and chromosome segregation errors can lead to cell transformation. We hypothesize that the presence of these defects within infected dividing cells identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation. Here we demonstrate that infection with Chlamydia trachomatis is able to transform 3T3 cells in soft agar resulting in anchorage independence and increased colony formation. Additionally, we show for the first time Chlamydia infects actively replicating cells in vivo. Infection of mice with Chlamydia results in significantly increased cell proliferation within the cervix, and in evidence of cervical dysplasia. Confocal examination of these infected tissues also revealed elements of chlamydial induced chromosome instability. These results contribute to a growing body of data implicating a role for Chlamydia in cervical cancer development and suggest a possible molecular mechanism for this effect.

Chlamydia trachomatis Inclusion Disrupts Host Cell Cytokinesis to Enhance Its Growth in Multinuclear Cells

“…It has been well documented that C. trachomatis infection can lead to host cell multinucleation by disrupting host cytokinesis through disruption of furrow ingression or abscission [Greene and Zhong, ; Sun et al, ; Brown et al, ]. Moreover, a recent study has shown that C. muridarum can infect actively replicating host cells in a mouse model [Knowlton et al, ]. Our study is the first to demonstrate that there is a physiological benefit for C. trachomatis to block host mitosis.…”

Chlamydia Trachomatis Infection-Associated Risk of Cervical Cancer

“…In the same line of evidence it was shown that infection of mice with C. trachomatis resulted in significantly increased cell proliferation, within the cervix, and in evidence of cervical dysplasia. 39 …”

Chlamydia cell biology and pathogenesis

“…induce anchorage- independent growth in mouse fibroblasts, a phenotype that correlates closely with tumorigenicity 119 . These phenotypes seem to be relevant in vivo as infection of the mouse cervix increases cervical cell proliferation, signs of cervical dysplasia and chromosome abnormalities 119 . Even eukaryotic cells that are cleared of Chlamydia spp.…”