title: Analysis of the Staphylococcus aureus abscess proteome identifies antimicrobial host proteins and bacterial stress responses at the host-pathogen interface.
abstract: Abscesses are a hallmark of invasive staphylococcal infections and the site of a dynamic struggle between pathogen and host. However, the precise host and bacterial factors that contribute to abscess formation and maintenance have not been completely described. In this work, we define the Staphylococcus aureus abscess proteome from both wild-type and neutropenic mice to elucidate the host response to staphylococcal infection and uncover novel S. aureus virulence factors. Among the proteins identified, the mouse protein histone H4 was enriched in the abscesses of wild-type compared with neutropenic animals. Histone H4 inhibits staphylococcal growth in vitro demonstrating a role for this protein in the innate immune response to staphylococcal infection. These analyses also identified staphylococcal proteins within the abscess, including known virulence factors and proteins with previously unrecognized roles in pathogenesis. Within the latter group was the universal stress protein Usp2, which was enriched in kidney lesions from neutropenic mice and required for the S. aureus response to stringent stress. Taken together, these data describe the S. aureus abscess proteome and lay the foundation for the identification of contributors to innate immunity and bacterial pathogenesis.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.|Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Cassat
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Sheg O
authors.initials: SO
authors.lastname: Aranmolate
authors.affiliation: Department of Biochemistry, Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Zimmerman
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.|Division of Animal Care, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA eric.skaar@vanderbilt.edu.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D000038:Abscess / Q000382:microbiology* / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D007155:Immunologic Factors / Q000032:analysis; D051379:Mice; D020543:Proteome / Q000032:analysis*; D012867:Skin / Q000737:chemistry* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D037521:Virulence Factors / Q000032:analysis
chemical_list: D007155:Immunologic Factors; D020543:Proteome; D037521:Virulence Factors
keywords: Staphylococcus aureus; innate immunity; pathogenesis; proteomics