Metabolic Adaptation of Staphylococcus aureus to Low-Respiratory Conditions Encountered During Invasive Infection Public Deposited

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  • March 19, 2019
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  • Vitko, Nicholas
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • Staphylococcus aureus is one of several Staphylococcus species that colonizes human skin. Several of these Staphylococcus species are also capable of causing human disease, including S. aureus. However, S. aureus infections occur far more frequently, exhibit greater variability in their presentation, and are generally much more severe. The widely recognized explanation for this observation is that S. aureus has acquired a large number of unique toxins and adhesins that promote enhanced tissue penetration and destruction. Our results support a complementary hypothesis: that S. aureus has metabolically adapted to invasive infection. Importantly, inflamed tissue spaces exhibit low levels of oxygen, low levels of free iron, and high levels of nitric oxide. These factors contribute to the inhibition of bacterial respiration. We show that S. aureus exhibits enhanced non-respiratory growth compared to other pathogenic Staphylococci and identify S. aureus acquisition of unique carbohydrate transporters and fermentative metabolic genes as the primary mechanism by which these divergent phenotypes have arisen. We then demonstrate that several of these unique metabolic genes contribute to S. aureus virulence in animal models of infection. Our data implicate metabolic adaptation to invasion infection as one mechanism responsible for the speciation of S. aureus from other skin-colonizing Staphylococci and implicate the host metabolic state as a contributing factor to S. aureus pathogenesis.
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  • In Copyright
Advisor
  • Moorman, Nathaniel
  • Goldman, William
  • Makowski, Liza
  • Richardson, Anthony
  • Kawula, Thomas
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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