Staphylococcus aureus-induced G2/M phase transition delay in host epithelial cells increases bacterial infective efficiency

• Published in: PloS one 2013-05, Vol.8 (5), p.e63279-e63279
• Main Authors: Alekseeva, Ludmila, Rault, Lucie, Almeida, Sintia, Legembre, Patrick, Edmond, Valérie, Azevedo, Vasco, Miyoshi, Anderson, Even, Sergine, Taieb, Frédéric, Arlot-Bonnemains, Yannick, Le Loir, Yves, Berkova, Nadia
• Format: Article
• Language: English
• Subjects: Accumulation; Analysis; Animals; Apoptosis; B cells; Bacteria; Biology; Cattle; CDC2 Protein Kinase - metabolism; Cell cycle; Cell growth; Cell lines; Cell number; Cell Proliferation; Cell Size; Cellular Biology; Colonization; Cyclin-dependent kinase; Cytometry; Delay; Deoxyribonucleic acid; DNA; E coli; Enlargement; Epithelial cells; Epithelial Cells - enzymology; Epithelial Cells - microbiology; Epithelial Cells - physiology; Escherichia coli; Etiology; Flow cytometry; G2 phase; G2 Phase Cell Cycle Checkpoints; Gene expression; Health aspects; HeLa Cells; Histone H3; Histones - metabolism; Homeotherms; Host-Pathogen Interactions; Humans; Infection; Kinases; Life Sciences; Medicine; Mitosis; Mitotic Index; Opportunist infection; Pathogens; Phase transitions; Phosphorylation; Protein Processing, Post-Translational; Science; Staphylococcus aureus; Staphylococcus aureus - pathogenicity; Staphylococcus aureus - physiology; Staphylococcus aureus infections; Staphylococcus infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063279

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.