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

Area of Science:

• Microbiology
• Biomedical Engineering
• Medical Imaging

Background:

• Pneumonia diagnosis requires rapid pathogen detection in the human lung.
• Previous antimicrobial peptide (AMP) probes showed limitations in ex vivo detection.
• Developing targeted imaging agents is crucial for diagnosing lung infections.

Purpose of the Study:

• To chemically modify an AMP (Ubiquicidin fragment 29-41) into a dendrimeric structure (NBD-UBI_dend) for enhanced in situ pathogen detection.
• To evaluate the specificity, efficacy, and safety of NBD-UBI_dend for imaging bacterial and fungal pathogens in human lung tissue.
• To demonstrate real-time, in situ visualization of pathogens within explanted human lungs.

Main Methods:

• Chemical modification of Ubiquicidin (UBI_29-41) into a tri-branched dendrimeric scaffold (NBD-UBI_dend).
• In vitro and ex vivo testing of NBD-UBI_dend for bacterial and fungal labelling specificity and signal enhancement.
• Assessment of NBD-UBI_dend toxicity and robustness in inflamed biological environments.
• Intrapulmonary delivery and optical endomicroscopy for in situ pathogen detection in explanted human lungs.

Main Results:

• The dendrimeric AMP (NBD-UBI_dend) exhibited enhanced signal amplification compared to its monomeric form.
• NBD-UBI_dend specifically labelled a broad range of pathogenic bacteria and Aspergillus fumigatus.
• The agent demonstrated high signal-to-noise ratio, did not label host cells, and was non-toxic.
• Real-time, in situ detection of bacteria was achieved in explanted human Cystic Fibrosis lungs.

Conclusions:

• Dendrimeric modification of AMPs significantly improves their performance for pathogen imaging.
• NBD-UBI_dend is a promising, non-toxic imaging agent for specific, rapid, in situ detection of lung pathogens.
• This technology holds potential for advancing the diagnosis of pneumonia and other lung infections.