TY - JOUR
T1 - Molecular detection of Gram-positive bacteria in the human lung through an optical fiber–based endoscope
AU - Mills, Bethany
AU - Megia-Fernandez, Alicia
AU - Norberg, Dominic
AU - Duncan, Sheelagh
AU - Marshall, Adam
AU - Akram, Ahsan R.
AU - Quinn, Thomas
AU - Young, Irene
AU - Bruce, Annya M.
AU - Scholefield, Emma
AU - Williams, Gareth O.S.
AU - Krstajić, Nikola
AU - Choudhary, Tushar R.
AU - Parker, Helen E.
AU - Tanner, Michael G.
AU - Harrington, Kerrianne
AU - Wood, Harry A.C.
AU - Birks, Timothy A.
AU - Knight, Jonathan C.
AU - Haslett, Christopher
AU - Dhaliwal, Kevin
AU - Bradley, Mark
AU - Ucuncu, Muhammed
AU - Stone, James M.
N1 - Funding Information:
Open Access funding provided by University of Edinburgh. We would like to thank Engineering and Physical Sciences Research Council (EPSRC, United Kingdom) Interdisciplinary Research Collaboration grant EP/K03197X/1 and EP/R005257/1.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Bacteria
KW - Fluorescence
KW - Gram-positive
KW - Lung
KW - Optical endomicroscopy
KW - Optical imaging
UR - http://www.scopus.com/inward/record.url?scp=85090764799&partnerID=8YFLogxK
U2 - 10.1007/s00259-020-05021-4
DO - 10.1007/s00259-020-05021-4
M3 - Article
C2 - 32915268
AN - SCOPUS:85090764799
SN - 1619-7070
VL - 48
SP - 800
EP - 807
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 3
ER -