title: Chlamydia trachomatis infection causes mitotic spindle pole defects independently from its effects on centrosome amplification.
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.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Knowlton
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brown
authors.forename: Theresa S
authors.initials: TS
authors.lastname: Richards
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Andreolas
authors.forename: Rahul K
authors.initials: RK
authors.lastname: Patel
authors.forename: Scott S
authors.initials: SS
authors.lastname: Grieshaber
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000378:metabolism*; D002690:Chlamydia Infections / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D056744:Cyclin B1 / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D064249:Securin; D008941:Spindle Apparatus / Q000378:metabolism* / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000821:virology
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D056744:Cyclin B1; C050045:NUMA1 protein, human; D009363:Neoplasm Proteins; D034521:Nuclear Matrix-Associated Proteins; D011993:Recombinant Fusion Proteins; D064249:Securin; D004398:Dyneins