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

Area of Science:

• Microbiology
• Immunology
• Bacterial Pathogenesis

Background:

• Staphylococcus aureus utilizes cell wall-anchored adhesins, including microbial surface component recognizing adhesive matrix molecule (MSCRAMM) family proteins like SdrD, for colonization and infection.
• These adhesins play crucial roles in host-pathogen interactions and bacterial virulence.

Purpose of the Study:

• To investigate the specific role of SdrD in Staphylococcus aureus survival and evasion of the innate immune system, particularly in the context of human whole blood.
• To determine if SdrD independently contributes to bacterial virulence and immune evasion.

Main Methods:

• Deletion mutagenesis of the sdrD gene in Staphylococcus aureus subsp. aureus strain NCTC8325-4.
• Assessment of bacterial survival in human whole blood ex vivo, with and without recombinant SdrD protein.
• Heterologous expression of SdrD in Lactococcus lactis to evaluate its independent function.
• In vivo virulence assessment using a murine intravenous infection model.

Main Results:

• Deletion of sdrD attenuated bacterial survival in human whole blood, correlating with increased neutrophil-mediated killing.
• Recombinant SdrD protein and heterologous expression of SdrD conferred protection against innate immune killing in human blood, independent of other S. aureus factors.
• In vivo studies showed reduced recovery of ΔsdrD mutants compared to the parent strain in blood and organs, indicating impaired virulence.

Conclusions:

• SdrD is a key contributor to Staphylococcus aureus survival within the host, particularly in the bloodstream.
• SdrD actively inhibits innate immune-mediated killing, representing a novel immune evasion mechanism.
• Targeting SdrD could be a potential strategy to combat Staphylococcus aureus infections.