Format

Send to

Choose Destination
FASEB J. 2015 May;29(5):1950-9. doi: 10.1096/fj.14-260513. Epub 2015 Feb 3.

Phenol-soluble modulin α induces G2/M phase transition delay in eukaryotic HeLa cells.

Author information

1
*Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1253 STLO, Rennes, France; Agrocampus Ouest, Unité Mixtes de Recherche1253 STLO, Rennes, France; Instituto de Ciências Biológicas- Universidade Federal de Minas Gerais , Belo Horizonte- Minas Gerais, Brazil; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Centre National de la Recherche Scientifique Unité Mixtes de Recherche5308, Université Lyon 1, Lyon, France; Hospices Civil de Lyon, Lyon, France; Laboratory of Human Bacterial Pathogenesis, National Institutes of Health, Bethesda, Maryland, USA; and **Microbial Genetics, University of Tübingen, Tübingen, Germany.
2
*Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1253 STLO, Rennes, France; Agrocampus Ouest, Unité Mixtes de Recherche1253 STLO, Rennes, France; Instituto de Ciências Biológicas- Universidade Federal de Minas Gerais , Belo Horizonte- Minas Gerais, Brazil; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Centre National de la Recherche Scientifique Unité Mixtes de Recherche5308, Université Lyon 1, Lyon, France; Hospices Civil de Lyon, Lyon, France; Laboratory of Human Bacterial Pathogenesis, National Institutes of Health, Bethesda, Maryland, USA; and **Microbial Genetics, University of Tübingen, Tübingen, Germany nadia.berkova@rennes.inra.fr.

Abstract

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 PSMα1 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 LAC∆psmα, 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.

KEYWORDS:

Staphylococcus aureus; cell cycle alteration; defensins; innate immune response; toxin

PMID:
25648996
PMCID:
PMC4771068
DOI:
10.1096/fj.14-260513
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center