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Rapid  in situ  detection of pathogens coupled with high resolution imaging in the distal human lung has the potential to provide new insights and diagnostic utility in patients in whom pneumonia is suspected. We have previously described an antimicrobial peptide (AMP) Ubiquicidin (fragment UBI 29–41 ) labelled with an environmentally sensitive fluorophore that optically detected bacteria  in vitro  but not  ex vivo . Here, we describe further chemical development of this compound and demonstrate that altering the secondary structure of the AMP to generate a tri-branched dendrimeric scaffold provides enhanced signal  in vitro  and  ex vivo  and consequently allows the rapid detection of pathogens  in situ  in an explanted human lung. This compound (NBD-UBI dend ) demonstrates bacterial labelling specificity for a broad panel of pathogenic bacteria and  Aspergillus fumigatus . NBD-UBI dend  demonstrated high signal-to-noise fluorescence amplification upon target engagement, did not label host mammalian cells and was non-toxic and chemically robust within the inflamed biological environment. Intrapulmonary delivery of NBD-UBI dend , coupled with optical endomicroscopy demonstrated real-time,  in situ  detection of bacteria in explanted whole human Cystic Fibrosis lungs.

Enhanced avidity from a multivalent fluorescent antimicrobial peptide enables pathogen detection in a human lung model