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Infect Immun. 2014 Nov;82(11):4889-98. doi: 10.1128/IAI.02328-14. Epub 2014 Sep 2.

Vaccine protection of leukopenic mice against Staphylococcus aureus bloodstream infection.

Author information

1
Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
2
Department of Microbiology, University of Chicago, Chicago, Illinois, USA dmissiak@bsd.uchicago.edu.

Abstract

The risk for Staphylococcus aureus bloodstream infection (BSI) is increased in immunocompromised individuals, including patients with hematologic malignancy and/or chemotherapy. Due to the emergence of antibiotic-resistant strains, designated methicillin-resistant S. aureus (MRSA), staphylococcal BSI in cancer patients is associated with high mortality; however, neither a protective vaccine nor pathogen-specific immunotherapy is currently available. Here, we modeled staphylococcal BSI in leukopenic CD-1 mice that had been treated with cyclophosphamide, a drug for leukemia and lymphoma patients. Cyclophosphamide-treated mice were highly sensitive to S. aureus BSI and developed infectious lesions lacking immune cell infiltrates. Virulence factors of S. aureus that are key for disease establishment in immunocompetent hosts-α-hemolysin (Hla), iron-regulated surface determinants (IsdA and IsdB), coagulase (Coa), and von Willebrand factor binding protein (vWbp)-are dispensable for the pathogenesis of BSI in leukopenic mice. In contrast, sortase A mutants, which cannot assemble surface proteins, display delayed time to death and increased survival in this model. A vaccine with four surface antigens (ClfA, FnBPB, SdrD, and SpAKKAA), which was identified by genetic vaccinology using sortase A mutants, raised antigen-specific immune responses that protected leukopenic mice against staphylococcal BSI.

PMID:
25183728
PMCID:
PMC4249340
DOI:
10.1128/IAI.02328-14
[Indexed for MEDLINE]
Free PMC Article

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