Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 10, Issue 464, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aal0033
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Funding
- Wellcome Trust
- Department of Health Healthcare Innovation Challenge Fund [HICF-0510-069]
- Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration Proteus [EP/K03197X/1]
- National Institute for Health Research (NIHR) BRC GMP Unit at Guy's and St. Thomas' NHS Foundation Trust
- NIHR Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust
- King's College London
- EPSRC [EP/K03197X/1] Funding Source: UKRI
- MRC [MR/J010901/1, G0800969] Funding Source: UKRI
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Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination of the presence, localization, and abundance of bacteria is critical for positive resolution of the infections and could be used for patient stratification and for monitoring treatment efficacy. Here, we developed an in situ approach to visualize Gram-negative bacterial species and cellular infiltrates in distal human lungs in real time. We used optical endomicroscopy to visualize a water-soluble optical imaging probe based on the antimicrobial peptide polymyxin conjugated to an environmentally sensitive fluorophore. The probe was chemically stable and nontoxic and, after in-human intrapulmonary microdosing, enabled the specific detection of Gram-negative bacteria in distal human airways and alveoli within minutes. The results suggest that pulmonary molecular imaging using a topically administered fluorescent probe targeting bacterial lipid A is safe and practical, enabling rapid in situ identification of Gram-negative bacteria in humans.
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