Soluble factor produced by [i]Staphylococcus aureus[/i] modulates the cell cycle of eukaryotic cells.

[i]Staphylococcus aureus[/i] can cause life-threatening infections such as bacteremia, pneumonia, osteomyelitis, endocarditis and sepsis. Epithelial cells are able to sense microbes, creating an early line of defense. We investigated S. aureus-host epithelial cells interaction using multidisciplinary approaches. Bacteria slowed down cell proliferation and induced a cytopathic effect. We observed an enlargement of host cells at MOI (Multiplicity of Infection) 20:1, which started being visible from 72h post-infection. Increasing MOI to 100:1 resulted in the induction of apoptosis. Using flow cytometry analysis, we demonstrated that S. aureus induces a G2/M phase delay in synchronized HeLa cells, which was associated with accumulation of the cyclin-dependent kinase Cdk1/cdc2, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a dramatic reduction of the mitotic cell number. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. Culture supernatants of S. aureus strains induced a similar G2/M phase transition delay, suggesting a soluble factor is involved in the transient cell cycle arrest. 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. Our findings reveal 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 host cell cycle alteration.