Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope

Mills, Bethany; Megia-Fernandez, Alicia; Norberg, Dominic; Duncan, Sheelagh; Marshall, Adam; Akram, Ahsan R.; Quinn, Thomas; Young, Irene; Bruce, Annya M.; Scholefield, Emma; Williams, Gareth O. S.; Krstajić, Nikola; Choudhary, Tushar R.; Parker, Helen E.; Tanner, Michael G.; Harrington, Kerrianne; Wood, Harry A. C.; Birks, Timothy A.; Knight, Jonathan C.; Haslett, Christopher; Dhaliwal, Kevin; Bradley, Mark; Ucuncu, Muhammed; Stone, James M.

PURPOSE: The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, a better understanding of bacterial colonization and infection. To facilitate this, we developed a highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, and specific visualization of Gram-positive bacteria through a bespoke optical fiber–based delivery/imaging endoscopic device. METHODS: We rationally designed a no-wash, red, Gram-positive-specific molecular imaging agent (Merocy-Van) based on vancomycin and an environmental merocyanine dye. We demonstrated the specificity and utility of the imaging agent in escalating in vitro and ex vivo whole human lung models (n = 3), utilizing a bespoke fiber–based delivery and imaging device, coupled to a wide-field, two-color endomicroscopy system. RESULTS: The imaging agent (Merocy-Van) was specific to Gram-positive bacteria and enabled no-wash imaging of S. aureus within the alveolar space of whole ex vivo human lungs within 60 s of delivery into the field-of-view, using the novel imaging/delivery endomicroscopy device. CONCLUSION: This platform enables the rapid and specific detection of Gram-positive bacteria in the human lung. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-020-05021-4) contains supplementary material, which is available to authorized users.