The cyclomodulin Cif of Photorhabdus luminescens inhibits insect cell proliferation and triggers host cell death by apoptosis |
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| Authors: | Carolina Varela Chavez Grégory Jubelin Gabriel Courties Aurélie Gomard Nadège Ginibre Sylvie Pages Frédéric Taïeb Pierre-Alain Girard Eric Oswald Alain Givaudan Robert Zumbihl Jean-Michel Escoubas |
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| Affiliation: | 1. INRA, UMR 1133, Laboratoire EMIP, Montpellier, France;2. Université Montpellier 2, UMR 1133, Laboratoire EMIP, Montpellier, France;3. INRA, UMR 1225, Toulouse, France;4. Université de Toulouse, ENVT, UMR 1225, Toulouse, France;1. Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, 371, av. du Doyen Gaston Giraud – 34295, Montpellier cedex 5, France;2. MACVIA-LR, European Innovation Partnership on Active and Healthy Ageing Reference Site, University Hospital of Montpellier, 371, av. du Doyen Gaston Giraud – 34295, Montpellier cedex 5, France;3. Section of Allergy and Clinical Immunology, Imperial College London, National Heart & Lung Institute, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK;4. Sorbonne Universités, UPMC Paris 06, UMR-S 1136, IPLESP, Equipe EPAR, F-75013, 4, Place Jussieu – 75005 Paris, France;1. Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China;2. Key Laboratory of Women’s Reproductive Health of Zhejiang Province, China;3. Key Laboratory of Reproductive Genetics of the Ministry of Education, China;1. Department of Molecular Biology, Laboratory of Molecular Parasitology, W. Stefanski Institute of Parasitology, Polish Academy of Sciences, 51/55 Twarda, 00-818 Warsaw, Poland;2. Laboratory of Molecular Biology, Mabion, 17 Fabryczna, 90-344 Lodz, Poland;3. Division of Parasitology, Department of Preclinical Sciences, Warsaw University of Life Sciences, 8 Ciszewskiego, 02-786 Warsaw, Poland;4. Laboratory of Transcriptional Regulation, Institute for Medical Biology of Polish Academy of Sciences, 106 Lodowa, 93-232 Lodz, Poland |
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| Abstract: | Cycle inhibiting factors (Cif) constitute a broad family of cyclomodulins present in bacterial pathogens of invertebrates and mammals. Cif proteins are thought to be type III effectors capable of arresting the cell cycle at G2/M phase transition in human cell lines. We report here the first direct functional analysis of CifPl, from the entomopathogenic bacterium Photorhabdus luminescens, in its insect host. The cifPl gene was expressed in P. luminescens cultures in vitro. The resulting protein was released into the culture medium, unlike the well characterized type III effector LopT. During locust infection, cifPl was expressed in both the hemolymph and the hematopoietic organ, but was not essential for P. luminescens virulence. CifPl inhibited proliferation of the insect cell line Sf9, by blocking the cell cycle at the G2/M phase transition. It also triggered host cell death by apoptosis. The integrity of the CifPl catalytic triad is essential for the cell cycle arrest and pro-apoptotic activities of this protein. These results highlight, for the first time, the dual role of Cif in the control of host cell proliferation and apoptotic death in a non-mammalian cell line. |
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