title: Identifying methicillin-resistant Staphylococcus aureus (MRSA) lung infections in mice via breath analysis using secondary electrospray ionization-mass spectrometry (SESI-MS).
abstract: Invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious health threat, causing an estimated 11,000 deaths per year in the United States. MRSA pneumonias account for 16% of invasive infections, and can be difficult to detect as the current state-of-the-art diagnostics require that bacterial DNA is recovered from the infection site. Because 60% of patients with invasive infections die within 7 d of culturing positive for MRSA, earlier detection of the pathogen may significantly reduce mortality. We aim to develop breath-based diagnostics that can detect Staphylococcal lung infections rapidly and non-invasively, and discriminate MRSA and methicillin-sensitive S. aureus (MSSA), in situ. Using a murine lung infection model, we have demonstrated that secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting can be used to robustly identify isogenic strains of MRSA and MSSA in the lung 24 h after bacterial inoculation. Principal components analysis (PCA) separates MRSA and MSSA breathprints using only the first component (p < 0.001). The predominant separation in the PCA is driven by shared peaks, low-abundance peaks, and rare peaks, supporting the use of biomarker panels to enhance the sensitivity and specificity of breath-based diagnostics.
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Bean
authors.affiliation: Northwest Metabolomics Research Center, University of Washington School of Medicine, 850 Republican Street, Room S140, Seattle, WA 98109, USA.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755, USA.
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Sengle
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Hill
mesh_terms: D000818:Animals; D001944:Breath Tests / Q000379:methods*; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification*; D051379:Mice; D008810:Mice, Inbred C57BL; D025341:Principal Component Analysis; D012141:Respiratory Tract Infections / Q000175:diagnosis* / Q000382:microbiology*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000382:microbiology*