Research ArticleRESPIRATORY DISEASES

In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A

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Science Translational Medicine  24 Oct 2018:
Vol. 10, Issue 464, eaal0033
DOI: 10.1126/scitranslmed.aal0033

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Lung infection in real time

Lung infections are frequent causes of complications in mechanically ventilated and immunosuppressed patients. However, the diagnosis is challenging, requires risky procedures, and is time consuming. Now, Akram et al. have developed an imaging method that is able to detect Gram-negative bacteria in real time in the distal part of the human lung. Using a fluorescent probe binding to lipid A, a molecule expressed on Gram-negative bacterial membranes, in combination with an optical endomicroscope, the researchers rapidly detected Gram-negative infections in distal airways in hospitalized individuals. The results suggest that the approach could accelerate the diagnosis of bacterial lung infection and facilitate the evaluation of antibiotic treatment efficacy.

Abstract

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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