Fungal colonization in Cystic Fibrosis (CF): Epidemiology and antifungal resistance in a French cohort of CF patients – Focused on Aspergillus fumigatus colonization

Introduction: Cystic fibrosis (CF) is the major genetic inherited disease in the European Caucasian population, with an average of 1 in 3000 living births in France. Prognostic depend essentially on the lung impairments. While considerable attention therefore has been paid over recent decades to prevent and treat bacterial respiratory infections, we observed emergence of fungi colonization in CF respiratory tract. In particular, Aspergillus fumigatus represents the most common causative agent colonizing the airways of CF patients; it can be responsible for Allergic Bronchopulmonary Aspergillosis (ABPA). Since oral corticosteroids and itraconazole represent the mainstay of ABPA treatment, long-term therapy may increase the risk of acquired resistance to azoles that is mainly associated with amino acid substitutions in the CYP51A gene of A. fumigatus. Objective: First, we managed to have exhaustive epidemiological data on species of filamentous fungi able to colonize the airway tract of 300 CF patients followed-up in our national prospective study ("MucoFong" study – PHRC1902). Second, CF patients being chronically exposed to azole (especially to itraconazole), our study aimed to evaluate the prevalence of azole resistance in isolates prospectively collected from CF patients followed-up in seven French hospitals involved in our national prospective study. Third, we focused on the most prevalent species: Aspergillus fumigatus, studying the azole resistance at molecular level. To our knowledge, it is the first multicenter study focused on azole resistance of A. fumigatus in CF. Methods: A total of 243 sputa were analyzed using the same protocol in each centre. The MICs of antifungal drugs were evaluated for each isolate using the E-test ® strips. Focusing on A. fumigatus, a total of 87 isolates was collected in 85 patients. These isolates were characterized at the molecular level by targeting ITS, ß-tubulin and MAT-A/α genes. The CYP51A gene as well as its promoter was sequenced; a 3D Cyp51A protein homology model was built. Results and discussion: 300 patients were enrolled in this study. At inclusion time, most of them were adults colonized with A. fumigatus (about 35% of the patients). Scedosporium was isolated in 5%, and Exophiala in about 2%. Regarding antifungal susceptibility, isolates of Scedosporium and Exophiala exhibited antifungal resistance comparable with published data. Regarding A. fumigatus, a majority of isolates (88.1%) were found sensitive to itraconazole (MIC≤ 2μg/ml), and 2 new mutations were identified and localized within 3-dimensional Cyp51A protein model. To obtain insight into azole resistance of A. fumigatus, the results are analyzed taking into account clinical data, itraconazole exposition, and the potential correlation between the identified CYP5IA mutations and azole resistance is discussed based on the Cyp51A protein homology model

A Carbon Nanofilament-Bead Necklace

Carbon nanofilaments with carbon beads grown on their surfaces were successfully synthesized reproducibly by a floating catalyst CVD method. The nanofilaments hosting the pearl-like structures typically show an average diameter of about 60 nm, which mostly consists of low-ordered graphite layers. The beads with diameter range 150−450 nm are composed of hundreds of crumpled and random graphite layers. The mechanism for the formation of these beaded nanofilaments is ascribed to two nucleation processes of the pyrolytic carbon deposition, arising from a temperature gradient between different parts of the reaction chamber. Furthermore, the Raman scattering properties of the beaded nanofilaments have been measured, as well as their confocal Raman G-line images. The Raman spectra reveal that that the trunks of the nanofilaments have better graphitic properties than the beads, which is consistent with the HRTEM analysis. The beaded nanofilaments are expected to have high potential applications in composites, which should exhibit both particle- and fiber-reinforcing functions for the host matrixes

Draft Genome Sequence of the Pathogenic Fungus Scedosporium apiospermum

This is the final version of the article. Available from the publisher via the DOI in this record.The first genome of one species of the Scedosporium apiospermum complex, responsible for localized to severe disseminated infections according to the immune status of the host, will contribute to a better understanding of the pathogenicity of these fungi and also to the discovery of the mechanisms underlying their low susceptibility to current antifungals.This work was supported by a grant (RF20120600725) from the association Vaincre la Mucoviscidose (France), which is gratefully acknowledged

Pneumocystis jirovecii colonization among cystic fibrosis patients: A French prospective multicenter study

Pneumocystis carriage was detected in 12.5% of 104 cystic fibrosis (CF) patients during a prospective multicenter French study, with a prevalence of genotype 85C/248C and geographic variations. It was significantly associated with the absence of P. aeruginosa colonization and better FEV1 values. Results are discussed considering the natural history of CF

Mechanical reinforcement of carbon foam by hafnium carbide deposit

Hafnium carbide made by chemical vapour deposition is being investigated as promising coating and mechanical reinforcement of carbon foams used at high temperature (above 3000°C). This substrate presents an exceptionally high open porosity (98 %) with a characteristic size of 65 pores per inch. The chemical composition of HfC deposit are determined by both electrical resistivity and Auger electron spectroscopy. The experimental conditions leading to an uniform thickness coating on the reticulated open cell foam are optimized. The evaluation and measurements of the reinforcement effect of such a coating on carbon foam properties are studied by compressive mechanical testing at room temperature and 2500°C