Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Multimodal Tracking of Controlled Staphylococcus aureus Infections in Mice
Welling, Mick M. ; Korne, Clarize M. De; Spa, Silvia J. ; Willigen, Danny M. Van; Hensbergen, Albertus W. ; Bunschoten, Anton ; Duszenko, Nikolas ; Smits, Wiep Klaas ; Roestenberg, Meta ; Leeuwen, Fijs W.B. Van - \ 2019
Bmc Infectious Diseases 5 (2019)7. - ISSN 1471-2334 - p. 1160 - 1168.
bacterial infection - cell-tracking - fluorescence - multimodal - SPECT - ubiquicidin

There is a need to develop diagnostic and analytical tools that allow noninvasive monitoring of bacterial growth and dissemination in vivo. For such cell-tracking studies to hold translational value to controlled human infections, in which volunteers are experimentally colonized, they should not require genetic modification, and they should allow tracking over a number of replication cycles. To gauge if an antimicrobial peptide tracer, 99m Tc-UBI 29-41 -Cy5, which contains both a fluorescent and a radioactive moiety, could be used for such in vivo bacterial tracking, we performed longitudinal imaging of a thigh-muscle infection with 99m Tc-UBI 29-41 -Cy5-labeled Staphylococcus aureus. Mice were imaged using SPECT and fluorescence-imaging modalities at various intervals during a 28 h period. Biodistribution analyses were performed to quantitate radioactivity in the abscess and other tissues. SPECT and fluorescence imaging in mice showed clear retention of the 99m Tc-UBI 29-41 -Cy5-labeled bacteria following inoculation in the thigh muscle. Despite bacterial replication, the signal intensity in the abscess only modestly decreased within a 28 h period: 52% of the total injected radioactivity per gram of tissue (%ID/g) at 4 h postinfection (pi) versus 44%ID/g at 28 h pi (15% decrease). After inoculation, a portion of the bacteria disseminated from the abscess, and S. aureus cultures were obtained from radioactive urine samples. Bacterial staining with 99m Tc-UBI 29-41 -Cy5 allowed noninvasive bacterial-cell tracking during a 28 h period. Given the versatility of the presented bacterial-tracking method, we believe that this concept could pave the way for precise imaging capabilities during controlled-human-infection studies.

Fluorescent imaging of bacterial infections and recent advances made with multimodal radiopharmaceuticals
Welling, Mick M. ; Hensbergen, Albertus W. ; Bunschoten, Anton ; Velders, Aldrik H. ; Scheper, Henk ; Smits, Wiep Klaas ; Roestenberg, Meta ; Leeuwen, Fijs W.B. van - \ 2019
Clinical and Translational Imaging 7 (2019)2. - ISSN 2281-5872 - p. 125 - 138.
Bacterial infection - Fluorescence imaging - Infectious diseases - Molecular imaging - Radioactivity

Background: Today, both radioactive SPECT and PET imaging radiopharmaceuticals are used for clinical diagnosis of bacterial infections. Due to the possible applications in image-guided surgery, fluorescent imaging of infections has gained interest. We here present the highlights and recent developments in the use of fluorescence imaging for bacterial infections. In this overview, we also include the latest developments in multimodal bacterial imaging strategies that combine radioactive and fluorescent imaging. Based on this literature, we present our future perspectives for the field including the translational potential. Methods: In the current review, we complement earlier reports with the most recent fluorescent and multimodal radiopharmaceuticals for bacterial infection imaging. Where possible, in this review, the chemical structure of the compounds and clinical images were shown. Results: A total of 35 out of 77 original articles on pre-clinical and clinical imaging of bacterial infections with fluorescent tracers and multimodality radiopharmaceuticals were included for reviewing. Conclusion: In our view, the highest translational potential lies with compounds that are based on targeting vectors that are specific for bacteria: e.g., fluorescently labelled UBI 29–41 , polymyxin B, vancomycin, ZnDPA and a M. tuberculosis-specific β-lactamase-cleavable linker CNIP800. Multimodal concepts using dually labelled UBI 29–41 , vancomycin, and ZnDPA help connect optical imaging to the more traditional use of radiopharmaceuticals in infectious diseases. Multimodal bacterial imaging is a promising strategy not only to diagnose bacterial infections but also to evaluate the effectivity of surgical treatment for infections.

An update on radiotracer development for molecular imaging of bacterial infections
Welling, Mick M. ; Hensbergen, Albertus W. ; Bunschoten, Anton ; Velders, Aldrik H. ; Roestenberg, Meta ; Leeuwen, Fijs W.B. van - \ 2019
Clinical and Translational Imaging 7 (2019)2. - ISSN 2281-5872 - p. 105 - 124.
Infectious diseases - Molecular imaging - Nuclear medicine - Pathogens - Radiotracers

Background: Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections—including the identification of bacterial species—is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes. Aim: In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers. Methods: The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown. Results: In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99m Tc- and 68 Ga-labelled UBI 29–41 , 99m Tc-vancomycin, m-[ 18 F]-fluoro-PABA, [methyl- 11 C]-D-methionine, [ 18 F]-FDS, [ 18 F]-maltohexaose and [ 18 F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings. Conclusion: This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.

UVA1 radiation inhibits calcineurin through oxidative damage mediated by photosensitization
Musson, R.E.A. ; Hensbergen, P.J. ; Westphal, A.H. ; Temmink, W.P.M. ; Deelder, A.M. ; Pelt, J. van; Mullenders, L.H.F. ; Smit, N.P.M. - \ 2011
Free Radical Biology and Medicine 50 (2011)10. - ISSN 0891-5849 - p. 1392 - 1399.
singlet molecular-oxygen - light-emission measurements - transcription factor nfat - human skin fibroblasts - kappa-b activity - hydrogen-peroxide - cyclosporine-a - ultraviolet-radiation - phosphatase-activity - human keratinocytes
The protein phosphatase calcineurin has been gradually revealing itself as the central controller of our immune response, although it is involved in a wide array of signaling pathways related to cellular development and cell cycle progression. As such, calcineurin is an attractive, yet delicate, therapeutic target for the prevention of allograft rejection and treatment of several inflammatory skin conditions. However, calcineurin activity is not only sensitive to immunosuppressants such as cyclosporin A and tacrolimus, but also subject to modulation by reactive oxygen species. We have recently shown, both in vivo and in vitro, that UVA1 radiation suppresses calcineurin activity. In this paper, we present evidence that this activity loss is due to singlet oxygen and superoxide generated by photosensitization and show that a closely related phosphatase, PP2A, is not affected. Furthermore, a survey of this damage reveals oxidation of several Met and Cys residues as well as an overall conformational change. These findings provide a mechanistic basis for the hypothesis that UVA1 and calcineurin inhibitors both affect the same signal transduction pathway in skin.
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