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Phenol‐soluble modulin α induces G2/M phase transition delay in eukaryotic HeLa cells
Author(s) -
Deplanche Martine,
Filho Rachid Aref ElAouar,
Alekseeva Ludmila,
Ladier Emilie,
Jardin Julien,
Henry Gwénaële,
Azevedo Vasco,
Miyoshi Anderson,
Beraud Laetitia,
Laurent Frederic,
Lina Gerard,
Vandenesch François,
Steghens JeanPaul,
Le Loir Yves,
Otto Michael,
Götz Friedrich,
Berkova Nadia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-260513
Subject(s) - phenol , hela , chemistry , phase transition , transition (genetics) , phase (matter) , microbiology and biotechnology , biology , biochemistry , organic chemistry , cell , physics , gene , quantum mechanics
Staphylococcus aureus is a gram‐positive bacterium responsible for a wide range of infections. Host cell cycle alteration is a sophisticated mechanism used by pathogens to hijack the defense functions of host cells. We previously demonstrated that S. aureus MW2 (USA400) bacteria induced a G2/M phase transition delay in HeLa cells. We demonstrate here that this activity is triggered by culture supernatant compounds. Using size exclusion chromatography of the MW2 supernatant, followed by mass spectroscopy analysis of corresponding peaks, we identified phenol‐soluble modulin α (PSMα) peptides as the likely candidates for this effect. Indeed, synthetic PSMα 1 and PSMα3 caused a G2/M phase transition delay. The implication of PSMα in cell cycle alteration was confirmed by comparison of S. aureus Los Angeles County clone (LAC) wild‐type with the isogenic mutant LACΔpsmα , which lacks the psmα operon encoding PSMα1‐4. PSMα‐induced G2/M transition delay correlated with a decrease in the defensin genes expression suggesting a diminution of antibacterial functions of epithelial cells. By testing the supernatant of S. aureus human clinical isolates, we found that the degree of G2/M phase transition delay correlated with PSMα1 production. We show that PSMs secreted by S. aureus alter the host cell cycle, revealing a newly identified mechanism for fostering an infection.—Deplanche, M., Filho. R. A. E.‐A., Alekseeva, L., Ladier, E., Jardin, J., Henry, G., Azevedo, V., Miyoshi, A., Beraud, L., Laurent, F., Lina, G., Vandenesch, F., Steghens, J.‐P., Le Loir, Y., Otto, M., Götz, F., Berkova, N. Phenol‐soluble modulin α induces G2/M phase transition delay in eukaryotic HeLa cells. FASEB J. 29, 1950‐1959 (2015). www.fasebj.org