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

<div><p><em>Chlamydia</em> are Gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. <em>Chlamydia trachomatis</em> 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 <em>Chlamydia</em> as a cofactor in cervical cancer formation. Here we demonstrate that infection with <em>Chlamydia trachomatis</em> is able to transform 3T3 cells in soft agar resulting in anchorage independence and increased colony formation. Additionally, we show for the first time <em>Chlamydia</em> infects actively replicating cells <em>in vivo</em>. Infection of mice with <em>Chlamydia</em> 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 <em>Chlamydia</em> in cervical cancer development and suggest a possible molecular mechanism for this effect.</p>