Stress-induced inactivation of the Staphylococcus aureus purine biosynthesis repressor leads to hypervirulence

Mariya I. Goncheva, Ronald S. Flannagan, Brigid E. Sterling, Holly A. Laakso, Nancy C. Friedrich, Julienne C. Kaiser, David W. Watson, Christy H. Wilson, Jessica R. Sheldon, Martin J. McGavin, Patti K. Kiser and David E. Heinrichs ()
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Mariya I. Goncheva: University of Western Ontario
Ronald S. Flannagan: University of Western Ontario
Brigid E. Sterling: University of Western Ontario
Holly A. Laakso: University of Western Ontario
Nancy C. Friedrich: University of Western Ontario
Julienne C. Kaiser: University of Western Ontario
David W. Watson: University of Western Ontario
Christy H. Wilson: University of Western Ontario
Jessica R. Sheldon: University of Western Ontario
Martin J. McGavin: University of Western Ontario
Patti K. Kiser: University of Western Ontario
David E. Heinrichs: University of Western Ontario

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Staphylococcus aureus is a significant cause of human infection. Here, we demonstrate that mutations in the transcriptional repressor of purine biosynthesis, purR, enhance the pathogenic potential of S. aureus. Indeed, systemic infection with purR mutants causes accelerated mortality in mice, which is due to aberrant up-regulation of fibronectin binding proteins (FnBPs). Remarkably, purR mutations can arise upon exposure of S. aureus to stress, such as an intact immune system. In humans, naturally occurring anti-FnBP antibodies exist that, while not protective against recurrent S. aureus infection, ostensibly protect against hypervirulent S. aureus infections. Vaccination studies support this notion, where anti-Fnb antibodies in mice protect against purR hypervirulence. These findings provide a novel link between purine metabolism and virulence in S. aureus.

Date: 2019
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DOI: 10.1038/s41467-019-08724-x

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