Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

Author:

Askarian Fatemeh1,Uchiyama Satoshi2,Valderrama J. Andrés2,Ajayi Clement1,Sollid Johanna U. E.1,van Sorge Nina M.3,Nizet Victor2,van Strijp Jos A. G.3,Johannessen Mona1

Affiliation:

1. Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway

2. Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California, USA

3. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands

Abstract

ABSTRACT Staphylococcus aureus expresses a panel of cell wall-anchored adhesins, including proteins belonging to the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) family, exemplified by the serine-aspartate repeat protein D (SdrD), which serve key roles in colonization and infection. Deletion of sdrD from S. aureus subsp. aureus strain NCTC8325-4 attenuated bacterial survival in human whole blood ex vivo , which was associated with increased killing by human neutrophils. Remarkably, SdrD was able to inhibit innate immune-mediated bacterial killing independently of other S. aureus proteins, since addition of recombinant SdrD protein and heterologous expression of SdrD in Lactococcus lactis promoted bacterial survival in human blood. SdrD contributes to bacterial virulence in vivo , since fewer S. aureus subsp. aureus NCTC8325-4 Δ sdrD bacteria than bacteria of the parent strain were recovered from blood and several organs using a murine intravenous infection model. Collectively, our findings reveal a new property of SdrD as an important key contributor to S. aureus survival and the ability to escape the innate immune system in blood.

Funder

Research council of Norway

NWO-VIDI

NIH grant

Helse Nord RHF

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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