Strains of Staphylococcus aureus that Colonize and Infect Skin Harbor Mutations in Metabolic Genes

Karen P Acker; Tania Wong Fok Lung; Emily West; Joshua Craft; Apurva Narechania; Hannah Smith; Kelsey O'Brien; Ahmed M Moustafa; Christine Lauren; Paul J Planet; Alice Prince

doi:10.1016/j.isci.2019.07.037

Strains of Staphylococcus aureus that Colonize and Infect Skin Harbor Mutations in Metabolic Genes

iScience. 2019 Sep 27:19:281-290. doi: 10.1016/j.isci.2019.07.037. Epub 2019 Jul 26.

Authors

Affiliations

¹ Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
² Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, USA.
³ Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁴ Department of Dermatology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
⁵ Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, USA; Department of Pediatrics, Perelman College of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶ Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: asp7@cumc.columbia.edu.

Abstract

Staphylococcus aureus is the most common cause of skin and soft tissue infections, yet the bacterial genetic changes associated with adaptation to human skin are not well characterized. S. aureus strains isolated from patients with chronic skin colonization and intermittent infection were used to determine the staphylococcal genotypes or phenotypes associated with adaptation to human skin. We demonstrate that polymorphisms in metabolic genes, particularly those involved in the tricarboxylic acid cycle, the fumarate-succinate axis, and the generation of terminal electron transporters, are unexpectedly common. These skin-adapted strains activated glycolysis and hypoxia-inducible factor-1α, interleukin (IL)-1β, and IL-18 release from keratinocytes and promoted dermatopathology equivalent to a methicillin-resistant Staphylococcus aureus USA300 control in a murine model of infection. However, in contrast to USA300, a skin-adapted isolate failed to generate protection from a secondary infectious challenge. Within the context of human skin, there appears to be selection for S. aureus metabolic adaptive changes that promote glycolysis and maintain pathogenicity.

Keywords: Bacteriology; Microbial Genetics; Microbiome.

Abstract

Grants and funding