title: Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.
abstract: 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.
authors: Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, North Carolina, USA.
authors: Sun Hee
authors: SH
authors: Ahn
authors: Ephraim L
authors: EL
authors: Tsalik
authors: Derek D
authors: DD
authors: Cyr
authors: Yurong
authors: Y
authors: Zhang
authors: Jennifer C
authors: JC
authors: van Velkinburgh
authors: Raymond J
authors: RJ
authors: Langley
authors: Seth W
authors: SW
authors: Glickman
authors: Charles B
authors: CB
authors: Cairns
authors: Aimee K
authors: AK
authors: Zaas
authors: Emanuel P
authors: EP
authors: Rivers
authors: Ronny M
authors: RM
authors: Otero
authors: Tim
authors: T
authors: Veldman
authors: Stephen F
authors: SF
authors: Kingsmore
authors: Joseph
authors: J
authors: Lucas
authors: Christopher W
authors: CW
authors: Woods
authors: Geoffrey S
authors: GS
authors: Ginsburg
authors: Vance G
authors: VG
authors: Fowler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D020869:Gene Expression Profiling / Q000145:classification / Q000379:methods*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents