-
Something wrong with this record ?
Biomimetic Analogues of the Desferrioxamine E Siderophore for PET Imaging of Invasive Aspergillosis: Targeting Properties and Species Specificity
A. Mular, I. Hubmann, M. Petrik, K. Bendova, B. Neuzilova, M. Aguiar, P. Caballero, A. Shanzer, H. Kozłowski, H. Haas, C. Decristoforo, E. Gumienna-Kontecka
Language English Country United States
Document type Journal Article
- MeSH
- Aspergillus fumigatus * metabolism chemistry MeSH
- Aspergillosis * diagnostic imaging microbiology MeSH
- Biomimetic Materials chemistry metabolism MeSH
- Peptides, Cyclic MeSH
- Deferoxamine chemistry MeSH
- Species Specificity MeSH
- Mice MeSH
- Positron-Emission Tomography * methods MeSH
- Gallium Radioisotopes * chemistry MeSH
- Siderophores * chemistry metabolism MeSH
- Staphylococcus aureus * metabolism MeSH
- Ferric Compounds chemistry MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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.
Department of Nuclear Medicine Medical University Innsbruck A 6020 Innsbruck Austria
Department of Organic Chemistry The Weizmann Institute of Science Rehovot 7610001 Israel
Faculty of Chemistry University of Wrocław 50 383 Wrocław Poland
Institute of Molecular Biology Biocenter Medical University Innsbruck A 6020 Innsbruck Austria
Public Higher Medical Professional School in Opole Katowicka 68 45 060 Opole Poland
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24019684
- 003
- CZ-PrNML
- 005
- 20241024110652.0
- 007
- ta
- 008
- 241015s2024 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1021/acs.jmedchem.4c00887 $2 doi
- 035 __
- $a (PubMed)38907990
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Mular, Andrzej $u Faculty of Chemistry, University of Wrocław, 50-383 Wrocław, Poland
- 245 10
- $a Biomimetic Analogues of the Desferrioxamine E Siderophore for PET Imaging of Invasive Aspergillosis: Targeting Properties and Species Specificity / $c A. Mular, I. Hubmann, M. Petrik, K. Bendova, B. Neuzilova, M. Aguiar, P. Caballero, A. Shanzer, H. Kozłowski, H. Haas, C. Decristoforo, E. Gumienna-Kontecka
- 520 9_
- $a 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.
- 650 12
- $a Aspergillus fumigatus $x metabolismus $x chemie $7 D001232
- 650 12
- $a pozitronová emisní tomografie $x metody $7 D049268
- 650 12
- $a siderofory $x chemie $x metabolismus $7 D017262
- 650 _2
- $a zvířata $7 D000818
- 650 12
- $a Staphylococcus aureus $x metabolismus $7 D013211
- 650 12
- $a aspergilóza $x diagnostické zobrazování $x mikrobiologie $7 D001228
- 650 12
- $a radioizotopy galia $x chemie $7 D005710
- 650 _2
- $a druhová specificita $7 D013045
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a železité sloučeniny $x chemie $7 D005290
- 650 _2
- $a biomimetické materiály $x chemie $x metabolismus $7 D040761
- 650 _2
- $a deferoxamin $x chemie $7 D003676
- 650 _2
- $a cyklické peptidy $7 D010456
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Hubmann, Isabella $u Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria
- 700 1_
- $a Petrik, Milos $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute, Palacky University, 77900 Olomouc, Czech Republic
- 700 1_
- $a Bendova, Katerina $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute, Palacky University, 77900 Olomouc, Czech Republic
- 700 1_
- $a Neuzilova, Barbora $u Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute, Palacky University, 77900 Olomouc, Czech Republic
- 700 1_
- $a Aguiar, Mario $u Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria $u Institute of Molecular Biology, Biocenter, Medical University Innsbruck, A-6020 Innsbruck, Austria
- 700 1_
- $a Caballero, Patricia $u Institute of Molecular Biology, Biocenter, Medical University Innsbruck, A-6020 Innsbruck, Austria $1 https://orcid.org/0009000519507690
- 700 1_
- $a Shanzer, Abraham $u Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 7610001, Israel
- 700 1_
- $a Kozłowski, Henryk $u Faculty of Chemistry, University of Wrocław, 50-383 Wrocław, Poland $u Public Higher Medical Professional School in Opole, Katowicka 68, 45-060 Opole, Poland
- 700 1_
- $a Haas, Hubertus $u Institute of Molecular Biology, Biocenter, Medical University Innsbruck, A-6020 Innsbruck, Austria
- 700 1_
- $a Decristoforo, Clemens $u Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria $1 https://orcid.org/0000000305664036
- 700 1_
- $a Gumienna-Kontecka, Elzbieta $u Faculty of Chemistry, University of Wrocław, 50-383 Wrocław, Poland $1 https://orcid.org/0000000295566378
- 773 0_
- $w MED00010049 $t Journal of medicinal chemistry $x 1520-4804 $g Roč. 67, č. 14 (2024), s. 12143-12154
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/38907990 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20241015 $b ABA008
- 991 __
- $a 20241024110646 $b ABA008
- 999 __
- $a ok $b bmc $g 2202112 $s 1231657
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 67 $c 14 $d 12143-12154 $e 20240622 $i 1520-4804 $m Journal of medicinal chemistry $n J Med Chem $x MED00010049
- LZP __
- $a Pubmed-20241015
