Staphylococcus aureus-induced G2-M phase transition delay in host epithelial cells increases bacterial infective efficiency.Reportar como inadecuado

Staphylococcus aureus-induced G2-M phase transition delay in host epithelial cells increases bacterial infective efficiency. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 STLO - Science et Technologie du Lait et de l-Oeuf 2 Department of General Biology 3 Récepteur de mort et échappement tumoral Irset - Institut de recherche, santé, environnement et travail Rennes 4 CPTP - Centre de physiopathologie de Toulouse Purpan 5 Cancer du rein : bases moléculaires de la tumorogenèse IGDR - Institut de Génétique et Développement de Rennes

Abstract : Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2-M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2-M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration.

Autor: Ludmila Alekseeva - Lucie Rault - Sintia Almeida - Patrick Legembre - Valérie Edmond - Vasco Azevedo - Anderson Miyoshi - Sergin



Documentos relacionados