A global view of Staphylococcus aureus whole genome expression upon internalization in human epithelial cells

Garzoni, Christian; Francois, Patrice; Huyghe, Antoine; Couzinet, Sabine; Tapparel, Caroline; Charbonnier, Yvan; Renzoni, Adriana; Lucchini, Sacha; Lew, Daniel P; Vaudaux, Pierre; Kelley, William L; Schrenzel, Jacques (2007). A global view of Staphylococcus aureus whole genome expression upon internalization in human epithelial cells. BMC Genomics, 8, p. 171. London: BioMed Central 10.1186/1471-2164-8-171

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BACKGROUND: Staphylococcus aureus, a leading cause of chronic or acute infections, is traditionally considered an extracellular pathogen despite repeated reports of S. aureus internalization by a variety of non-myeloid cells in vitro. This property potentially contributes to bacterial persistence, protection from antibiotics and evasion of immune defenses. Mechanisms contributing to internalization have been partly elucidated, but bacterial processes triggered intracellularly are largely unknown. RESULTS: We have developed an in vitro model using human lung epithelial cells that shows intracellular bacterial persistence for up to 2 weeks. Using an original approach we successfully collected and amplified low amounts of bacterial RNA recovered from infected eukaryotic cells. Transcriptomic analysis using an oligoarray covering the whole S. aureus genome was performed at two post-internalization times and compared to gene expression of non-internalized bacteria. No signs of cellular death were observed after prolonged internalization of Staphylococcus aureus 6850 in epithelial cells. Following internalization, extensive alterations of bacterial gene expression were observed. Whereas major metabolic pathways including cell division, nutrient transport and regulatory processes were drastically down-regulated, numerous genes involved in iron scavenging and virulence were up-regulated. This initial adaptation was followed by a transcriptional increase in several metabolic functions. However, expression of several toxin genes known to affect host cell integrity appeared strictly limited. CONCLUSION: These molecular insights correlated with phenotypic observations and demonstrated that S. aureus modulates gene expression at early times post infection to promote survival. Staphylococcus aureus appears adapted to intracellular survival in non-phagocytic cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Garzoni, Christian and Couzinet, Sabine

ISSN:

1471-2164

ISBN:

17570841

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:59

Last Modified:

04 Sep 2015 08:34

Publisher DOI:

10.1186/1471-2164-8-171

PubMed ID:

17570841

Web of Science ID:

000248122900001

BORIS DOI:

10.7892/boris.25688

URI:

https://boris.unibe.ch/id/eprint/25688 (FactScience: 60473)

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