title: Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood.
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 ΔsdrD 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.
authors: Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway fatemeh.askarian@uit.no mona.johannessen@uit.no.
authors: Fatemeh
authors: F
authors: Askarian
authors: Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California, USA.
authors: Satoshi
authors: S
authors: Uchiyama
authors: Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California, USA.
authors: J Andrés
authors: JA
authors: Valderrama
authors: Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors: Clement
authors: C
authors: Ajayi
authors: Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors: Johanna U E
authors: JUE
authors: Sollid
authors: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Nina M
authors: NM
authors: van Sorge
authors: Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California, USA.
authors: Victor
authors: V
authors: Nizet
authors: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jos A G
authors: JAG
authors: van Strijp
authors: Research Group of Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway fatemeh.askarian@uit.no mona.johannessen@uit.no.
authors: Mona
authors: M
authors: Johannessen
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D013294:Lactococcus lactis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011994:Recombinant Proteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000097:blood* / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; D011994:Recombinant Proteins; C115915:SdrD protein, Staphylococcus aureus
keywords: SdrD; neutrophils; systemic infection; virulence; whole blood