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

被引:36
作者
Askarian, Fatemeh [1 ]
Uchiyama, Satoshi [2 ,3 ]
Valderrama, J. Andres [2 ,3 ]
Ajayi, Clement [1 ]
Sollid, Johanna U. E. [1 ]
van Sorge, Nina M. [4 ]
Nizet, Victor [2 ,3 ]
van Strijp, Jos A. G. [4 ]
Johannessen, Mona [1 ]
机构
[1] Arctic Univ Norway, UiT, Res Grp Host Microbe Interact, Dept Med Biol,Fac Hlth Sci, Tromso, Norway
[2] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA
[3] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA
[4] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands
关键词
SdrD; virulence; neutrophils; systemic infection; whole blood; IMMUNE EVASION; SURFACE-PROTEINS; MEDIATED PHAGOCYTOSIS; HUMAN NEUTROPHILS; CLUMPING FACTOR; COMPLEMENT; BINDING; FIBRINOGEN; INFECTION; DISORDERS;
D O I
10.1128/IAI.00559-16
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.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.
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页数:11
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