title: Staphylococcus aureus-induced G2/M phase transition delay in host epithelial cells increases bacterial infective efficiency.
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.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Alekseeva
authors.forename: Lucie
authors.initials: L
authors.lastname: Rault
authors.forename: Sintia
authors.initials: S
authors.lastname: Almeida
authors.forename: Patrick
authors.initials: P
authors.lastname: Legembre
authors.forename: Valérie
authors.initials: V
authors.lastname: Edmond
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Sergine
authors.initials: S
authors.lastname: Even
authors.forename: Frédéric
authors.initials: F
authors.lastname: Taieb
authors.forename: Yannick
authors.initials: Y
authors.lastname: Arlot-Bonnemains
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Loir
authors.forename: Nadia
authors.initials: N
authors.lastname: Berkova
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation; D048429:Cell Size; D004847:Epithelial Cells / Q000201:enzymology / Q000382:microbiology* / Q000502:physiology; D059565:G2 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008938:Mitosis; D008940:Mitotic Index; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013211:Staphylococcus aureus / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D006657:Histones; D016203:CDC2 Protein Kinase