TY - JOUR
T1 - The Chlamydia trachomatis type III-secreted effector protein CteG induces centrosome amplification through interactions with centrin-2
AU - Steiert, Brianna
AU - Icardi, Carolina M.
AU - Faris, Robert
AU - McCaslin, Paige N.
AU - Smith, Parker
AU - Klingelhutz, Aloysius J.
AU - Yau, Peter M.
AU - Weber, Mary M.
N1 - ACKNOWLEDGMENTS. We thank Dr. Derek J. Fisher and Dr. Luís Jaime Mota for sharing the CteG-null strain (cteG::aadA). We also thank Dr. Jessica Sherry and Dr. Joanne Engel for assistance with troubleshooting centrosome staining and measurements. Additionally, we would like thank Weber lab members Isaias Herring for assistance with bacterial titering and Jabeena CA for technical support with protein purification and critical review of this manuscript. We acknowledge grant support from the NIH (B.S. T32 AI007511, M.M.W. R01 AI150812, R01 AI155434) and the University of Iowa Stead Family Scholars Program to M.M.W.
PY - 2023/5/16
Y1 - 2023/5/16
N2 - 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 bacterium Chlamydia trachomatis (C.t.) correlates with blocked cytokinesis, supernumerary centrosomes, and multipolar spindles; however, the mechanisms behind how C.t. induces these cellular abnormalities remain largely unknown. Here we show that the secreted effector protein, CteG, binds to centrin-2 (CETN2), a key structural component of centrosomes and regulator of centriole duplication. Our data indicate that both CteG and CETN2 are necessary for infection-induced centrosome amplification, in a manner that requires the C-terminus of CteG. Strikingly, CteG is important for in vivo infection and growth in primary cervical cells but is dispensable for growth in immortalized cells, highlighting the importance of this effector protein to chlamydial infection. These findings begin to provide mechanistic insight into how C.t. induces cellular abnormalities during infection, but also indicate that obligate intracellular bacteria may contribute to cellular transformation events. Centrosome amplification mediated by CteG–CETN2 interactions may explain why chlamydial infection leads to an increased risk of cervical or ovarian cancer.
AB - 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 bacterium Chlamydia trachomatis (C.t.) correlates with blocked cytokinesis, supernumerary centrosomes, and multipolar spindles; however, the mechanisms behind how C.t. induces these cellular abnormalities remain largely unknown. Here we show that the secreted effector protein, CteG, binds to centrin-2 (CETN2), a key structural component of centrosomes and regulator of centriole duplication. Our data indicate that both CteG and CETN2 are necessary for infection-induced centrosome amplification, in a manner that requires the C-terminus of CteG. Strikingly, CteG is important for in vivo infection and growth in primary cervical cells but is dispensable for growth in immortalized cells, highlighting the importance of this effector protein to chlamydial infection. These findings begin to provide mechanistic insight into how C.t. induces cellular abnormalities during infection, but also indicate that obligate intracellular bacteria may contribute to cellular transformation events. Centrosome amplification mediated by CteG–CETN2 interactions may explain why chlamydial infection leads to an increased risk of cervical or ovarian cancer.
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U2 - 10.1073/pnas.2303487120
DO - 10.1073/pnas.2303487120
M3 - Article
C2 - 37155906
AN - SCOPUS:85158081410
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
M1 - e2303487120
ER -