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A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
Identifying methicillin-resistant Staphylococcus aureus (MRSA) lung infections in mice via breath analysis using
Heather D Bean1, Jiangjiang Zhu2, Jackson C Sengle1
1Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755, USA.
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.
Insights
Early detection of Staphylococcus lung infections using breath analysis is crucial. New breathprinting technology can rapidly identify MRSA and MSSA, potentially reducing mortality from these serious infections.
Area of Science:
- Infectious Diseases
- Pulmonary Medicine
- Analytical Chemistry
Background:
- Invasive methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant mortality, with MRSA pneumonias being difficult to diagnose using current methods.
- Delayed diagnosis of MRSA infections, often requiring DNA recovery from infection sites, contributes to high mortality rates within days of positive cultures.
- There is a critical need for rapid, non-invasive diagnostic tools to detect and differentiate MRSA and methicillin-sensitive S. aureus (MSSA) lung infections.
Purpose of the Study:
- To develop and validate breath-based diagnostics for rapid, non-invasive detection of Staphylococcus lung infections.
- To differentiate between MRSA and MSSA infections in situ using breath analysis.
- To establish the feasibility of using breathprinting for early pathogen identification.
Main Methods:
- Utilized a murine lung infection model to simulate Staphylococcus aureus infections.
- Employed secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting for volatile organic compound analysis.
- Applied principal components analysis (PCA) to differentiate breathprints between MRSA and MSSA infected subjects.
Main Results:
- SESI-MS breathprinting successfully identified isogenic strains of MRSA and MSSA in the lung 24 hours post-inoculation.
- Principal components analysis robustly separated MRSA and MSSA breathprints based on specific peak patterns.
- The separation was driven by variations in shared, low-abundance, and rare peaks, indicating potential biomarker candidates.
Conclusions:
- Breathprinting via SESI-MS offers a promising non-invasive method for rapid detection and differentiation of MRSA and MSSA lung infections.
- Biomarker panels derived from breath analysis can enhance the sensitivity and specificity of these diagnostics.
- This approach has the potential to significantly reduce mortality associated with invasive Staphylococcus aureus lung infections through earlier diagnosis.

