Regard à travers le danio pour mieux comprendre les interactions hôte/pathogène

Bernut, Audrey; Lutfalla, Georges; Kremer, Laurent

doi:10.1051/medsci/20153106017

Cited by 6 publications

(6 citation statements)

References 39 publications

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“…For various reasons, the zebrafish embryo is particularly attractive in toxicology and pharmacology [3]. First, its transparency allows the visual detection of malformations, without interrupting development or invasive interventions [4]. Second, the number of eggs laid is high, and its development time is short [5].…”

Section: Introductionmentioning

confidence: 99%

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Siméon

Brotzmann

Fisher

et al. 2020

Reproductive Toxicology

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In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 hours post-fertilization. Chemicals' distribution is modeled in the cells, lysosomes, and mitochondria of ten organs of the embryo. The model's partition coefficients are calculated with sub-models using physicochemical properties of the chemicals of interest. The model accounts for organ growth and changes in metabolic clearance with time. We compared ab initio model predictions to data obtained on culture medium and embryo concentrations of valproic acid (VPA) and nine analogs during continuous dosing under the OECD test guideline 236. We further improved the predictions by estimating metabolic clearance and partition coefficients from the data by Bayesian calibration. We also assessed the performance of the model at reproducing data published by Brox et al. (2016) on VPA and 16 other chemicals. We finally compared dose-response relationships calculated for mortality and malformations on the basis of predicted whole embryo concentrations versus those based on nominal water concentrations. The use of target organ concentrations substantially shifted the magnitude of doseresponse parameters and the relative toxicity ranking of chemicals studied.

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Section: Introductionmentioning

confidence: 99%

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Siméon

Brotzmann

Fisher

et al. 2020

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…One example is the cording morphology of mycobacteria, which correspond to snake-like structures formed by the end-to-end and side-to-side aggregation of bacilli [ 29 ]. The formation of large bacterial aggregates impairs phagocytosis and is required for virulence [ 30 ]. Another well-documented strategy to escape host immunity is the formation of filaments after invasion of epithelial cells by uropathogenic E .…”

Section: Discussionmentioning

confidence: 99%

Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis

et al. 2017

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Enterococcus faecalis is an opportunistic pathogen frequently isolated in clinical settings. This organism is intrinsically resistant to several clinically relevant antibiotics and can transfer resistance to other pathogens. Although E. faecalis has emerged as a major nosocomial pathogen, the mechanisms underlying the virulence of this organism remain elusive. We studied the regulation of daughter cell separation during growth and explored the impact of this process on pathogenesis. We demonstrate that the activity of the AtlA peptidoglycan hydrolase, an enzyme dedicated to septum cleavage, is controlled by several mechanisms, including glycosylation and recognition of the peptidoglycan substrate. We show that the long cell chains of E. faecalis mutants are more susceptible to phagocytosis and are no longer able to cause lethality in the zebrafish model of infection. Altogether, this work indicates that control of cell separation during division underpins the pathogenesis of E. faecalis infections and represents a novel enterococcal virulence factor. We propose that inhibition of septum cleavage during division represents an attractive therapeutic strategy to control infections.

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“…ZF has a very similar cellular composition in innate immunity to humans, and their optical transparency allows non-invasive real-time monitoring of bacterial infection and host-pathogen interactions [18]. Furthermore, it is relatively simple and cost-effective [19]. Nonetheless, the ZF model has some obvious limitations when compared to mammalian models.…”

Section: -O-(carboxymethyl)-1-deoxy-14-dihydro-4-hydroxy1-oxorifamymentioning

confidence: 99%

Rifamycin O, An Alternative Anti-Mycobacterium abscessus Agent

et al. 2020

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Mycobacterium abscessus is the most difficult-to-treat nontuberculous mycobacteria because of its resistance to many antibiotics. In this study, we screened the Korea Chemical Bank library for a bioluminescent reporter assay to identify molecules capable of acting against M. abscessus. On application of the assay, rifamycin O showed excellent in vitro activity with a narrow range of the minimum inhibitory concentration required to inhibit the growth of 90% of the bacterium (MIC90 = 4.0–6.2 μM); its in vivo efficacy in the zebrafish (Danio rerio) infection model was comparable to that of rifabutin at 25 μM. Furthermore, rifamycin O did not show significant toxicity in cells and the zebrafish model. These results are the first in vivo indication that rifamycin O may be a drug candidate for treating M. abscessus infections.

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Regard à travers le danio pour mieux comprendre les interactions hôte/pathogène

Cited by 6 publications

References 39 publications

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis

Rifamycin O, An Alternative Anti-Mycobacterium abscessus Agent

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