title: 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.
authors: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America.
authors: Andrea E
authors: AE
authors: Knowlton
authors: Larry J
authors: LJ
authors: Fowler
authors: Rahul K
authors: RK
authors: Patel
authors: Shannon M
authors: SM
authors: Wallet
authors: Scott S
authors: SS
authors: Grieshaber
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018385:Centrosome / Q000473:pathology*; D002584:Cervix Uteri / Q000382:microbiology / Q000473:pathology*; D002690:Chlamydia Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D002692:Chlamydia trachomatis / Q000472:pathogenicity* / Q000502:physiology; D043171:Chromosomal Instability; D005260:Female; D051379:Mice; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000382:microbiology / Q000473:pathology*