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

Autor: Christine T. Lauren, Apurva Narechania, Joshua Craft, Emily S. West, Hannah Smith, Karen P. Acker, Kelsey O’Brien, Alice Prince, Paul J. Planet, Ahmed M Moustafa, Tania Wong Fok Lung
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: iScience, Vol 19, Iss, Pp 281-290 (2019)
iScience
ISSN: 2589-0042
Popis: Summary 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.
Graphical Abstract
Highlights • Staphylococcus aureus is a metabolically adaptive organism • Skin-adapted isolates harbor mutations in fumC and other metabolic genes • Novel metabolic gene variants were identified in skin-adapted strains
Bacteriology; Microbial Genetics; Microbiome
Databáze: OpenAIRE