Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

Published

Journal Article

Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

Full Text

Duke Authors

Cited Authors

  • Ahn, SH; Tsalik, EL; Cyr, DD; Zhang, Y; van Velkinburgh, JC; Langley, RJ; Glickman, SW; Cairns, CB; Zaas, AK; Rivers, EP; Otero, RM; Veldman, T; Kingsmore, SF; Lucas, J; Woods, CW; Ginsburg, GS; Fowler, VG

Published Date

  • January 9, 2013

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • e48979 -

PubMed ID

  • 23326304

Pubmed Central ID

  • 23326304

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0048979

Language

  • eng