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 |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Context (language use) Human skin 02 engineering and technology Biology medicine.disease_cause Article Microbiology 03 medical and health sciences Genotype medicine lcsh:Science Gene Multidisciplinary integumentary system Microbial Genetics Interleukin Bacteriology 021001 nanoscience & nanotechnology Phenotype 3. Good health 030104 developmental biology Staphylococcus aureus Microbial genetics lcsh:Q Microbiome 0210 nano-technology |
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 |
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