Lab

Dynamic

About the lab

Dynamic research group (EA 7380, UPEC, EnvA) comprises physicians and veterinarians who decided to collaborate to answer specific clinical questions or solve practice-related problems in relation with the colonisation and infection by fungal or bacterial pathogens in humans and animals.

Featured projects (1)

Project
Local immune response during pulmonar aspergillosis (A. fumigatus) on turkeys

Featured research (5)

Aspergillus fumigatus is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in A. fumigatus has changed treatment recommendations. The objective of this study was to evaluate the efficacy of voriconazole (VRZ) in a Galleria mellonella model of invasive infection due to azole-susceptible or azole-resistant A. fumigatus isolates. We also sought to describe the pharmacokinetics of VRZ in the G. mellonella model. G. mellonella larvae were infected with conidial suspensions of azole-susceptible and azole-resistant isolates of A. fumigatus. Mortality curves were used to calculate the lethal dose. Assessment of the efficacy of VRZ or amphotericin B (AMB) treatment was based on mortality in the lethal model and histopathologic lesions. The pharmacokinetics of VRZ were determined in larval hemolymph. Invasive fungal infection was obtained after conidial inoculation. A dose-dependent reduction in mortality was observed after antifungal treatment with AMB and VRZ. VRZ was more effective at treating larvae inoculated with azole-susceptible A. fumigatus isolates than larvae inoculated with azole-resistant isolates. The concentration of VRZ was maximal at the beginning of treatment and gradually decreased in the hemolymph to reach a Cmin (24 h) between 0.11 and 11.30 mg/L, depending on the dose. In conclusion, G. mellonella is a suitable model for testing the efficacy of antifungal agents against A. fumigatus.
Background Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. Methods We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. Findings Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39–3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12–6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14–4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26–2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53–3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03–2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0–72·8) versus 32·1% (27·7–36·7; p<0·0001). Interpretation This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. Funding Pfizer.
Across the world, many commercial poultry flocks and captive birds are threatened by infection with Aspergillus fumigatus. Susceptibility to aspergillosis varies among birds; among galliform birds specifically, morbidity and mortality rates seem to be greater in turkeys than in chickens. Little is known regarding the features of avian immune responses after inhalation of Aspergillus conidia, and to date, scarce information on inflammatory responses during aspergillosis exists. Thus, in the present study, we aimed to improve our understanding of the interactions between A. fumigatus and economically relevant galliform birds in terms of local innate immune responses. Intra-tracheal aerosolization of A. fumigatus conidia in turkey and chicken poults led to more severe clinical signs and lung lesions in turkeys, but leukocyte recovery from lung lavages was higher in chickens at 1dpi only. Interestingly, only chicken CD8+ T lymphocyte proportions increased after infection. Furthermore, the lungs of infected chickens showed an early upregulation of pro-inflammatory cytokines, including IL-1β, IFN-γ and IL-6, whereas in turkeys, most of these cytokines showed a downregulation or a delayed upregulation. These results confirmed the importance of an early pro-inflammatory response to ensure the development of an appropriate anti-fungal immunity to avoid Aspergillus dissemination in the respiratory tract. In conclusion, we show for the first time that differences in local innate immune responses between chickens and turkeys during aspergillosis may determine the outcome of the disease. Lay summary: Aspergillus fumigatus infection may cause mortality in poultry, depending on species sensitivity. This study confirms the earlier activation of chickens' pro-inflammatory effectors to control Aspergillus dissemination, whereas turkeys' immune response enables the exacerbation of lung lesions.
Background: Scabies is a frequent cutaneous infection caused by the mite Sarcoptes scabiei in a large number of mammals including humans. As the resistance of S. scabiei against several chemical acaricides has been previously documented, the establishment of alternative and effective control molecules is required. Objectives: In this study, the potential acaricidal activity of beauvericin was assessed against different life stages of S. scabiei var. suis and, in comparison with dimpylate and ivermectin, two commercially available molecules used for the treatment of S. scabiei infection in animals and/or humans. Methods: The toxicity of beauvericin against cultured human fibroblast skin cells was evaluated using an MTT proliferation assay. In our in vitro model, developmental stages of S. scabiei have been placed in Petri dishes filled with Columbia agar supplemented with pig serum and different concentrations of the drugs. Results: Cell sensitivity assays demonstrated low toxicity of beauvericin against primary human fibroblast skin cells. At 0.5 and 5 mM, beauvericin showed higher activity against adults and eggs of S. scabiei when compared to dimpylate and ivermectin. Conclusion: These results revealed that the use of beauvericin is promising and might be considered for the treatment of S. scabiei infection.

Lab head

Francoise Botterel
Department
  • Microbiology

Members (8)

Eric Dannaoui
  • Assistance Publique – Hôpitaux de Paris
Charlotte Bernigaud
  • Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor), Service de Dermatologie
Francoise Foulet
  • Université Paris-Est Créteil Val de Marne - Université Paris 12
Cécile Angebault
  • CHU Henri Mondor, Assistance Publique – Hôpitaux de Paris
Veronica Risco-Castillo
  • École Nationale Vétérinaire d'Alfort
Jessica Beser
  • Public Health Agency of Sweden
Pascal arné
  • École Nationale Vétérinaire d'Alfort
Olivier Chosidow
Olivier Chosidow
  • Not confirmed yet
Grégory Jouvion
Grégory Jouvion
  • Not confirmed yet
Jean-Winoc Decousser
Jean-Winoc Decousser
  • Not confirmed yet
Paul-Louis Woerther
Paul-Louis Woerther
  • Not confirmed yet
Cateau Estelle
Cateau Estelle
  • Not confirmed yet
Sana Jemel
Sana Jemel
  • Not confirmed yet
Paul Louis Woerther
Paul Louis Woerther
  • Not confirmed yet
Laude Adrien
Laude Adrien
  • Not confirmed yet