The pathogenic fungus Aspergillus fumigatus utilizes a cyclic ferrioxamine E (FOXE) siderophore to acquire iron from the host. Biomimetic FOXE analogues were labeled with gallium-68 for molecular imaging with PET. [68Ga]Ga(III)-FOXE analogues were internalized in A. fumigatus cells via Sit1. Uptake of [68Ga]Ga(III)-FOX 2-5, the most structurally alike analogue to FOXE, was high by both A. fumigatus and bacterial Staphylococcus aureus. However, altering the ring size provoked species-specific uptake between these two microbes: ring size shortening by one methylene unit (FOX 2-4) increased uptake by A. fumigatus compared to that by S. aureus, whereas lengthening the ring (FOX 2-6 and 3-5) had the opposite effect. These results were consistent both in vitro and in vivo, including PET imaging in infection models. Overall, this study provided valuable structural insights into the specificity of siderophore uptake and, for the first time, opened up ways for selective targeting and imaging of microbial pathogens by siderophore derivatization.
- MeSH
- Aspergillus fumigatus * metabolismus chemie MeSH
- aspergilóza * diagnostické zobrazování mikrobiologie MeSH
- biomimetické materiály chemie metabolismus MeSH
- cyklické peptidy MeSH
- deferoxamin chemie MeSH
- druhová specificita MeSH
- myši MeSH
- pozitronová emisní tomografie * metody MeSH
- radioizotopy galia * chemie MeSH
- siderofory * chemie metabolismus MeSH
- Staphylococcus aureus * metabolismus MeSH
- železité sloučeniny chemie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
