The ArlRS two-component system is a regulator of Staphylococcus aureus-induced endothelial cell damage
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Staphylococcus aureus endovascular infections retain a high morbidity and mortality despite antibiotics and supportive care. The destruction of endothelial cells (ECs) is a critical step in the pathogenesis of S. aureus endovascular infections. In order to better understand S. aureus-induced EC damage, we systematically screened a collection of two-component regulatory system mutants of methicillin-resistant S. aureus (MRSA) USA300 strain JE2 for damage induction in human umbilical vein ECs (HUVECs). This screen revealed that the two-component regulatory system ArlRS is required for maximum damage: arlRS inactivation leads to a > 70% reduction in damage. In a different genetic S. aureus background (RN6390, MSSA strain) arlRS inactivation had a smaller but also significant effect on EC damage. In both strains, the reduction in EC damage was accompanied by a significant reduction in internalization. In conclusion, we determined a novel role of ArlRS in S. aureus-induced EC damage, which will help to better understand the pathogenesis of S. aureus endovascular infection.
We thank Esther Kleiner-Blatter (Department of Obstetrics, Zurich University Hospital, Switzerland) for her help with umbilical cords.
This work was supported by Grants of the Foundation for Research at the Medical Faculty, University of Zurich, Switzerland (to AZ and KS), a research Grant 2013 by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) (to KS), a Grant from the Novartis Foundation (to AZ) and from the Swiss National Science Foundation (310030_146295/1 to AZ).
Compliance with ethical standards
Conflict of Interest
The authors declare that they have no conflict of interest.
The study was conducted in compliance with the current version of the Declaration of Helsinki, as well as all national legal and regulatory requirements, and was approved by the cantonal ethics committee Zurich (KEK-StV-Nr.07/07).
Informed consent was obtained from all women donating umbilical cords.
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