Duality of liver and kidney lesions after systemic infection of immunosuppressed and immunocompetent mice with<i>Aspergillus fumigatus</i>

Jouvion, Grégory; Brock, Matthias; Droin-Bergère, Sabrina; Ibrahim-Granet, Oumaïma

doi:10.4161/viru.3.1.18654

Cited by 8 publications

(9 citation statements)

References 23 publications

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“…BLI thereby visualized the heterogeneity of targeted organs dependent on immune status, and the luminescence correlated well with histopathology. These studies confirmed the general suitability of the method to study the infection processes of pathogenic filamentous fungi (19).…”

supporting

confidence: 56%

“…A. fumigatus strain C3 was used in previous studies (17)(18)(19) and contains a P. pyralis luciferase gene from plasmid pSP-luc ϩ that is codon adapted to mammalian cells. To improve luciferase production levels accompanied by an increase in light emission, a synthetic codon-optimized version of the luciferase gene was generated (GenBank accession number KC677695).…”

Section: Methodsmentioning

confidence: 99%

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Assessment of Efficacy of Antifungals against Aspergillus fumigatus: Value of Real-Time Bioluminescence Imaging

Galiger

Brock

Jouvion

et al. 2013

Antimicrob Agents Chemother

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c Aspergillus fumigatus causes life-threatening infections, especially in immunocompromised patients. Common drugs for therapy of aspergillosis are polyenes, azoles, and echinocandins. However, despite in vitro efficacy of these antifungals, treatment failure is frequently observed. In this study, we established bioluminescence imaging to monitor drug efficacy under in vitro and in vivo conditions. In vitro assays confirmed the effectiveness of liposomal amphotericin B, voriconazole, and anidulafungin. Liposomal amphotericin B and voriconazole were fungicidal, whereas anidulafungin allowed initial germination of conidia that stopped elongation but allowed the conidia to remain viable. In vivo studies were performed with a leukopenic murine model. Mice were challenged by intranasal instillation with a bioluminescent reporter strain (5 ؋ 10 5 and 2.5 ؋ 10 5 conidia), and therapy efficacies of liposomal amphotericin B, voriconazole, and anidulafungin were monitored. For monotherapy, the highest treatment efficacy was observed with liposomal amphotericin B, whereas the efficacies of voriconazole and anidulafungin were strongly dependent on the infectious dose. When therapy efficacy was studied with different drug combinations, all combinations improved the rate of treatment success compared to that with monotherapy. One hundred percent survival was obtained for treatment with a combination of liposomal amphotericin B and anidulafungin, which prevented not only pulmonary infections but also infections of the sinus. In conclusion, combination therapy increases treatment success, at least in the murine infection model. In addition, our novel approach based on real-time imaging enables in vivo monitoring of drug efficacy in different organs during therapy of invasive aspergillosis.

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supporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Assessment of Efficacy of Antifungals against Aspergillus fumigatus: Value of Real-Time Bioluminescence Imaging

Galiger

Brock

Jouvion

et al. 2013

Antimicrob Agents Chemother

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“…Some A. fumigatus strains were selected for their very specific features like bioluminescent AfC3 (Brock et al, 2008; Ibrahim-Granet et al, 2010; Fekkar et al, 2012; Jouvion et al, 2012; Morisse et al, 2012) or Af 2/7/1 (Galiger et al, 2013; Savers et al, 2016). Among other examples, one should notice for instance AF91 (also maned NCPF 7100, IHEM 13936, or J960180) which expresses attenuated virulence (Denning et al, 1997a,b; Dannaoui et al, 1999; Overdijk et al, 1999; Warn et al, 2003, 2006, 2010; Paisley et al, 2005), or EMFR S678P that resists to echinocandins (Miyazaki et al, 1993; Lepak et al, 2013a,b,c) and AZN 58 for which flucytosin is not active (Verweij et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…Additional information were also provided by Panepinto et al when they explained how histopathological lesion areas were measured by using ScionImage® analysis software (Panepinto et al, 2003). Among the unusual miscellaneous methods for monitoring the course of infection, some investigators reported how useful could be in vivo imaging techniques based on bioluminescent A. fumigatus strain (Brock et al, 2008; Ibrahim-Granet et al, 2010; Fekkar et al, 2012; Jouvion et al, 2012), or antibody-guided positron emission tomography and magnetic resonance imaging (Rolle et al, 2016). The former requires luciferin as exogenous substrate, while the latter needs particular caution for radiation protection.…”

Section: Discussionmentioning

confidence: 99%

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Désoubeaux

Cray

2017

Front. Microbiol.

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Invasive aspergillosis has been studied in laboratory by the means of plethora of distinct animal models. They were developed to address pathophysiology, therapy, diagnosis, or miscellaneous other concerns associated. However, there are great discrepancies regarding all the experimental variables of animal models, and a thorough focus on them is needed. This systematic review completed a comprehensive bibliographic analysis specifically-based on the technical features of rodent models infected with Aspergillus fumigatus. Out the 800 articles reviewed, it was shown that mice remained the preferred model (85.8% of the referenced reports), above rats (10.8%), and guinea pigs (3.8%). Three quarters of the models involved immunocompromised status, mainly by steroids (44.4%) and/or alkylating drugs (42.9%), but only 27.7% were reported to receive antibiotic prophylaxis to prevent from bacterial infection. Injection of spores (30.0%) and inhalation/deposition into respiratory airways (66.9%) were the most used routes for experimental inoculation. Overall, more than 230 distinct A. fumigatus strains were used in models. Of all the published studies, 18.4% did not mention usage of any diagnostic tool, like histopathology or mycological culture, to control correct implementation of the disease and to measure outcome. In light of these findings, a consensus discussion should be engaged to establish a minimum standardization, although this may not be consistently suitable for addressing all the specific aspects of invasive aspergillosis.

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“…As described above, the currently available fungal BLI infection models include cutaneous, subcutaneous, vaginal, oropharyngeal, and invasive candidiasis caused by C. albicans [7], [13], [17], [18], as well as invasive and cutaneous aspergillosis due to A. fumigatus [8], [16]. In addition to the spatial and temporal visualization of the infectious Candida or Aspergillus reporters, BLI now offers the possibility to study a wide range of other host–pathogen interactions, such as biofilm formation [19], [20] or interactions related to the host immune response [21], [22]. Furthermore, BLI opens a new window in monitoring antifungal drug efficacy in different organs during therapy of candidiasis [7], [13], [23] and aspergillosis [10].…”

Section: What Can Be Monitored Using Fungal Infection Bli Models?mentioning

confidence: 99%

Illuminating Fungal Infections with Bioluminescence

et al. 2014

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Duality of liver and kidney lesions after systemic infection of immunosuppressed and immunocompetent mice withAspergillus fumigatus

Cited by 8 publications

References 23 publications

Assessment of Efficacy of Antifungals against Aspergillus fumigatus: Value of Real-Time Bioluminescence Imaging

Assessment of Efficacy of Antifungals against Aspergillus fumigatus: Value of Real-Time Bioluminescence Imaging

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Illuminating Fungal Infections with Bioluminescence

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