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.