Variable staphyloxanthin production by Staphylococcus aureus drives strain-dependent effects on diabetic wound-healing outcomes
Amy E. Campbell,
Amelia R. McCready-Vangi,
Aayushi Uberoi,
Sofía M. Murga-Garrido,
Victoria M. Lovins,
Ellen K. White,
Jamie Ting-Chun Pan,
Simon A.B. Knight,
Alexis R. Morgenstern,
Colleen Bianco,
Paul J. Planet,
Sue E. Gardner,
Elizabeth A. Grice
Affiliations
Amy E. Campbell
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Amelia R. McCready-Vangi
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Aayushi Uberoi
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Sofía M. Murga-Garrido
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Victoria M. Lovins
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Ellen K. White
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Jamie Ting-Chun Pan
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Simon A.B. Knight
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Alexis R. Morgenstern
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Colleen Bianco
Division of Infectious Disease, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Paul J. Planet
Division of Infectious Disease, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; Departments of Pediatrics and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Sue E. Gardner
College of Nursing, University of Iowa, Iowa City, IA 52242, USA
Elizabeth A. Grice
Departments of Dermatology and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Summary: Strain-level variation in Staphylococcus aureus is a factor that contributes to disease burden and clinical outcomes in skin disorders and chronic wounds. However, the microbial mechanisms that drive these variable host responses are poorly understood. To identify mechanisms underlying strain-specific outcomes, we perform high-throughput phenotyping screens on S. aureus isolates cultured from diabetic foot ulcers. Isolates from non-healing wounds produce more staphyloxanthin, a cell membrane pigment. In murine diabetic wounds, staphyloxanthin-producing isolates delay wound closure significantly compared with staphyloxanthin-deficient isolates. Staphyloxanthin promotes resistance to oxidative stress and enhances bacterial survival in neutrophils. Comparative genomic and transcriptomic analysis of genetically similar clinical isolates with disparate staphyloxanthin phenotypes reveals a mutation in the sigma B operon, resulting in marked differences in stress response gene expression. Our work illustrates a framework to identify traits that underlie strain-level variation in disease burden and suggests more precise targets for therapeutic intervention in S. aureus-positive wounds.
