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Staphylococcus aureus cells induce G2/M phase transition delay in the human and bovine epithelial cells.
Auteur(s) : Alekseeva, Ludmila Rault, Lucie ALMEIDA DA SILVA, SINTIA Edmond, Valérie Azevedo, Vasco Even, Sergine Arlot-Bonnemains, Yannick Le Loir, Yves
Auteurs secondaires : Russian Academy of Sciences Institut National de la Recherche Agronomique (INRA) Science et Technologie du Lait et de l'Oeuf (STLO) ; Institut National de la Recherche Agronomique (INRA) - AGROCAMPUS OUEST Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Université de Rennes 1 Universidade Federal de Minas Gerais Institut de Génétique et Développement de Rennes (IGDR) ; Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) INRA, Ambassade de France en Russie

Éditeur(s) : HAL CCSD
Résumé : Staphylococcus aureus is an opportunistic pathogen of humans and warm-blooded animals. It is foundin healthy carriage and can cause a wide range of infections in its hosts. The epithelial surface is theprincipal site of staphylococcal infection. The pathogens have evolved sophisticated mechanisms tohijack the main function of the host cells, thus promoting their invasion and colonization. Amongstthese effects are, alteration of host cell apoptosis, promotion of cell proliferation or conversely,inhibition of cell growth. Using human cervix cancer HeLa and mammary gland bovine MAC-Tepithelial cells, we studied the cytopathic effect of S. aureus and its ability to affect host cell cycle.Using microscopic examination, we found that S. aureus induced the cytopathic effect resulting in theenlargement of the host cells 72 hours post infection. Our experiments showed that the proliferationrate of the epithelial cells was slowed down in S. aureus-infected culture. Three different S. aureusstrains from human and animal origins were used and showed similar effect on both human and bovinecells. Microscopic analysis of DAPI-stained cells revealed huge decrease of mitotic indexes in infectedHeLa and Mac-T cells, synchronized by Double Thymidine Block. Using flow cytometry analysis, wefound that S. aureus induces G2/M phase delay in synchronous HeLa cells. By Western blot analysis,we showed that the G2/M phase delay was associated with accumulation of inactive phosphorylatedcyclin-dependent kinase Cdk1/cdc2, a key inducer of mitosis entry, and dephosphorylation of corehistone H3, an important component of the epigenetic landscape.These results suggest that the delay in G2/M phase transition of the infected epithelial cells may beone of the mechanisms employed by S. aureus to survive and to propagate inside the host. A fullcomprehension of the mechanisms associated to S. aureus-host cell interactions will undoubtedly helpto discover novel targets to treat staphylococcal infections.
EMBO
Villars sur Ollon, Switzerland

hal-01454214
https://hal.archives-ouvertes.fr/hal-01454214
PRODINRA : 171657

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