The centrosome is the main microtubule organizing center of the cell and is crucial for mitotic spindle assembly, chromosome segregation, and cell division. Centrosome duplication is tightly controlled, yet several pathogens, most notably oncogenic viruses, perturb this process leading to increased centrosome numbers. Infection by the obligate intracellular pathogen Chlamydia trachomatis (C.t.) correlates with blocked cytokinesis, supernumerary centrosomes, and multipolar spindles; however, the mechanisms behind how C.t. induces these cellular abnormalities from the confines of its inclusion, remain largely unknown. Here we show that the type III secreted effector protein, CteG, binds to centrin-2 (CETN2), a key structural component of centrosomes and regulator of centriole duplication. This interaction requires a functional calcium binding EF Hand-4 of CETN2, which is recognized via the C-terminus of CteG. Significantly, we show that deletion of CteG, or knockdown of CETN2, significantly impairs chlamydias ability to induce centrosome amplification. Uniquely, we have identified the first bacterial effector to target centrins, crucial regulators of the eukaryotic cell cycle. These findings have not only allowed us to begin addressing how C.t. induces gross cellular abnormalities during infection, but also indicate that obligate intracellular bacteria may contribute to cellular transformation events that negatively impact host physiology even when the pathogen is long removed. Understanding the consequences of CteG-CETN2 interactions, its impact on centrosome amplification, and the long-term effect this has on host cells could explain why chlamydial infection leads to an increased risk of cervical or ovarian cancer.
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