Mendive-Tapia Lorena, Zhao Can, Akram Ahsan R, Preciado Sara, Albericio Fernando, Lee Martin, Serrels Alan, Kielland Nicola, Read Nick D, Lavilla Rodolfo, Vendrell Marc
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, Barcelona 08028, Spain.
Manchester Fungal Infection Group, Institute of Inflammation and Repair, University of Manchester, CTF Building, Grafton St, Manchester M13 9NT, UK.
Nat Commun. 2016 Mar 9;7:10940. doi: 10.1038/ncomms10940.
Fluorescent antimicrobial peptides are promising structures for in situ, real-time imaging of fungal infection. Here we report a fluorogenic probe to image Aspergillus fumigatus directly in human pulmonary tissue. We have developed a fluorogenic Trp-BODIPY amino acid with a spacer-free C-C linkage between Trp and a BODIPY fluorogen, which shows remarkable fluorescence enhancement in hydrophobic microenvironments. The incorporation of our fluorogenic amino acid in short antimicrobial peptides does not impair their selectivity for fungal cells, and enables rapid and direct fungal imaging without any washing steps. We have optimized the stability of our probes in human samples to perform multi-photon imaging of A. fumigatus in ex vivo human tissue. The incorporation of our unique BODIPY fluorogen in biologically relevant peptides will accelerate the development of novel imaging probes with high sensitivity and specificity.
荧光抗菌肽是用于真菌感染原位实时成像的有前景的结构。在此,我们报告一种荧光探针,可直接在人肺组织中对烟曲霉进行成像。我们开发了一种荧光色氨酸 - 硼二吡咯氨基酸,在色氨酸和硼二吡咯荧光团之间具有无间隔的碳 - 碳连接,其在疏水微环境中显示出显著的荧光增强。将我们的荧光氨基酸掺入短抗菌肽中不会损害它们对真菌细胞的选择性,并且无需任何洗涤步骤就能实现快速直接的真菌成像。我们优化了探针在人体样本中的稳定性,以便对离体人体组织中的烟曲霉进行多光子成像。将我们独特的硼二吡咯荧光团掺入具有生物学相关性的肽中,将加速具有高灵敏度和特异性的新型成像探针的开发。