Les onychomycoses à moisissures

Onychomycoses represent about 30% of superficial mycosis that are encountered in Dermatology consults. Fungi such as dermatophytes, which are mainly found on the feet nails, cause nearly 50% of these onychopathies. Yeasts are predominantly present on hands, whereas non-dermatophytic moulds are very seldom involved in both foot and hand nails infections. According to literature, these moulds are responsible for 2 to 17% of onychomycoses. Nevertheless, we have to differentiate between onychomycoses due to pseudodermatophytes such as Neoscytalidium (ex-Scytalidium) and Onychocola canadensis, which present a high affinity for keratin, and onychomycoses due to filamentous fungi such as Aspergillus, Fusarium, Scopulariopsis, Acremonium… These saprophytic moulds are indeed most of the time considered as colonizers rather than real pathogens agents. Mycology and histopathology laboratories play an important role. They allow to identify the species that is involved in nail infection, but also to confirm parasitism by the fungus in the infected nails. Indeed, before attributing any pathogenic role to non-dermatophytic moulds, it is essential to precisely evaluate their pathogenicity through samples and accurate mycological and/or histological analysis. The treatment of onychomycoses due to non-dermatophytic moulds is difficult, as there is today no consensus. The choice of an antifungal agent will first depend on the species that is involved in the infection, but also on the severity of nail lesions and on the patient himself. In most cases, the onychomycosis will be cured with chemical or mechanical removing of the infected tissues, followed by a local antifungal treatment. In some cases, a systemic therapy will be discussed

Diagnostic biologique des candidoses

Candidiasis is the most common fungal infection in humans. Conventional techniques are usually sufficient for the diagnosis of superficial candidiasis. For deep-seated or systemic candidiasis, blood cultures still represent the “gold standard”, although their sensitivity can be overtaken. In recent decades, numerous alternative tests have been developed to overcome this lack of sensitivity. These techniques allow the detection of antibodies, antigens, metabolites or nucleic acids. In most cases, serological results have to be interpretated according to the immune status of patients. Detection of antibodies alone is often poorly contributive to the diagnosis, except when this is associated with the detection of circulating antigens. Thus, the detection of circulating mannans is useful in the diagnosis of infections caused by the most frequent Candida species; the sensitivity of this test increases with the repetition of samplings and the joint detection of anti-mannan antibodies. Besides, detection of β(1.3)-D glucans, alone or in association with the detection of mannans, may be useful for early diagnosis of deep-seated candidiasis. Molecular biology helps us to diagnose deep-seated candidiasis without referring to the patient\u27s immune status. With the newly commercialized kits, molecular detection of Candida should expand in laboratories. In the same way, proteomic analysis by MALDI-TOF allows to substantially shorten the time for identification of isolated yeasts. Modern methods of molecular typing, which are based on the analysis of genome variability, replaced phenotypic techniques. Although insufficiently standardized, they represent a powerful tool to better understand the epidemiology of Candida infections

Méthodes de diagnostic d’une onychomycose

Onychomycosis represents about 50% of ungueal pathology. Dermatophytes (especially Trichophyton rubrum and Trichophyton interdigitale) are the main species involved in tinea pedis. Yeasts of the Candida (Candida albicans, Candida parapsilosis,…) genus are predominant on hands and very often associated with ungueal disease and perionyxis. Fungi other than the classic dermatophytes and yeasts can be rarely isolated from nail diseases. Among them, species belonging to Scopulariopsis, Aspergillus and Fusarium genus are mainly found, but their involvement in the disease must be proved. Other fungi, presenting a special affinity to keratin (pseudodermatophytes), such as Neoscytalidium dimidiatum (ex Scytalidium dimidiatum) from tropical and subtropical areas and Onychocola canadensis from Northern America and Europe, are considered as real pathogens in nail diseases. A multidisciplinary approach, including clinicians and biologists, is required to confirm the mycosis. This comparative review emphasizes the importance of histological examination, as well as molecular approaches, which are very contributive to the diagnosis of onychomycosis. The role of the laboratory is to identify at the species level the fungus isolated from nail scrapings and to show its involvement in the ungueal lesions

Conventional Methods for the Diagnosis of Dermatophytosis

Dermatophytes are keratinolytic fungi responsible for a large variety of diseases that can affect glabrous skin, nails and hair. In many cases, the diagnosis is not clinically obvious, and mycological analysis is required. This includes both direct microscopic examination and cultures. First of all, clinical specimens have to be sampled according to localization and characteristics of the lesions. Direct microscopic examination is usually performed using clearing reagents (KOH or Amman’s chloral-lactophenol), but its sensitivity may be greatly enhanced by the use of stains or fluorochromes such as Congo red or Calcofluor white. Histological analysis is an efficient method, but it is constraining for the patients and, as direct examination, it does not allow precise identification of the pathogen. Cultures are therefore needed, and specific culture media may be used to overcome the growth of rapidly growing contaminating moulds which may hamper the recovery of dermatophytes. Identification at the species level which may be useful to initiate an appropriate treatment or for setting prophylactic measures, relies on macroscopic and microscopic morphology. Subcultures on culture media which stimulate conidiation and, for some species, the production of pigments, are often necessary. Additionally, in case of atypical isolates, some biochemical or physiological tests may be performed such as the search for urease activity or the in vitro hair perforation test. However, their contribution to species identification is rather limited, and progress is still needed for the development of biochemical or immunological tests allowing an accurate identification at the species level, pending for the availability of molecular biology-based kits

Wavelength-shifting light traps for SWGO and other applications

Wavelength-shifting (WLS) materials contain molecules that absorb light and reemit at longer wavelengths. They can be used for light detection because they provide a large effective area for low cost and they are able to efficiently trap and guide light because of total internal reflection processes. We are currently developing such a WLS detector, considering two main designs: A single-shift design with one wavelength shift (tile) and a double-shift design with two wavelength shifts (tile and fiber). As photodetectors we use small Silicon photomultipliers (SiPMs) with a high photon detection efficiency (PDE) and single-photon sensitivity. The double-shift layout goes at the expense of detection efficiency. In this design however, light is channeled to the two ends of a fiber, thus requiring a reduced photosensitive area compared to the single-shift layout. We will present the results of our measurements and show that light traps and SiPMs together represent a promising alternative to PMTs in case of a non-focused light beam. For the special case of SWGO, the application of light traps is also motivated by a possible improvement of the gamma/hadron separation, using a one-chamber tank with an array of wavelength-shifting light traps instead of a (two-chamber) tank with PMTs. Besides SWGO, new WLS detectors could also constitute useful and cheap technology for other experiments and use cases. The contribution summarizes our motivation and efforts to build a light trap detection module and to characterize its properties in terms of costs, temporal performance and detection efficiency.Comment: 8 pages, 9 figures, Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 202

Fungal respiratory infections in cystic fibrosis

International audienc

Émergence de nouveaux champignons pathogènes en médecine : revue générale

RésuméAu cours des 20 dernières années, l’incidence des infections fongiques, tant superficielles que profondes, a augmenté de façon considérable. Ces pathologies surviennent le plus souvent chez des patients fragilisés (transplantations d’organes, greffes de moelle, chimiothérapies aplasiantes, nouveaux immunosuppresseurs, …). Si les malades et les traitements ont évolué, les champignons impliqués dans les pathologies se sont, eux aussi, diversifiés. On observe en effet l’émergence d’espèces auparavant inconnues du milieu médical, ainsi que la réémergence d’espèces au pouvoir pathogène établi, mais qui sont responsables de nouvelles formes cliniques, survenant sur des terrains différents. Ces infections sont associées à des taux de mortalité élevés, souvent liés à un retard au diagnostic. La liste des « nouveaux champignons » isolés en pathologie humaine s’allonge ainsi chaque jour. Les nouveaux outils moléculaires ont permis d’identifier avec précision les différentes souches isolées. Mais les infections fongiques émergent aussi chez les sujets immunocompétents. Ainsi, la prévalence des mycoses à champignons « exotiques » augmente en zone d’endémie. Par ailleurs, de nombreux champignons filamenteux sont responsables de colonisation chronique des voies respiratoires chez les patients atteints d’affections respiratoires chroniques comme la mucoviscidose. Les onychomycoses sont également plus fréquentes dans la population générale, et on rapporte un nombre croissant de mycoses cutanées chez les sportifs. Le meilleur suivi des patients et la généralisation des dépistages systématiques contribuent certainement en grande partie à cette émergence. Les espèces rencontrées sont essentiellement des Ascomycètes ou des formes asexuées (Deutéromycètes) apparentées à ces derniers, plus rarement des Zygomycètes (Mucorales) et des Basidiomycètes. Nous passerons en revue les différents groupes de champignons : levures (Candida, Cryptococcus, …), filamenteux (Aspergillus, Fusarium, Scedosporium, Alternaria, Exophiala, …), dimorphiques (Histoplasma, Coccidioides, Penicillium marneffei, …) et les espèces assimilées d’intérêt médical, en insistant sur les espèces émergentes nouvellement décrites. Summary The incidence of fungal infections has significantly increased during the past two decades. These diseases mainly occur in susceptible patients (organ or bone marrow transplantation, haematological malignancies, immunosuppressive drugs, …). Patients and treatments have changed, as well as fungi which are involved in infections. Indeed, species that were previously unknown to the medical community are now emerging, likewise well known pathogenic species are now responsible for new clinical forms. Invasive fungal infections are associated with high mortality rates, often related to delayed diagnosis. The list of “new fungi” isolated in human is growing every day. Molecular tools allowed identifying these species. Fungal infections, however, are also emerging in immunocompetent patients. Thus, the prevalence of infections due to dimorphic fungi is increasing in endemic areas. Moreover, many filamentous fungi are responsible for chronic colonization of the airways in patients suffering from chronic respiratory diseases such as cystic fibrosis. Onychomycosis are also more frequent in the general population, and a growing number of skin mycosis is reported among athletes. The improved monitoring of patients and the widespread use of systematic screenings have probably largely contributed to this emergence. The species encountered mainly belong to Ascomycetes or to relative Deuteromycetes, less frequently to Zygomycetes or to Basidiomycetes. The different groups of fungi will be reviewed: yeasts (Candida, Cryptococcus, …), moulds (Aspergillus, Fusarium, Scedosporium, Alternaria, Exophiala, …), dimorphic fungi (Histoplasma, Coccidioides, Penicillium marneffei, …) and relative species of medical importance, with a special emphasis on emerging new species

Self-assembly of proteins into a three-dimensional multilayer system: investigation of the surface of the human fungal pathogen Aspergillus fumigatus.

Hydrophobins are small surface active proteins that fulfil a wide spectrum of functions in fungal growth and development. The human fungal pathogen Aspergillus fumigatus expresses RodA hydrophobins that self-assemble on the outer conidial surface into tightly organized nanorods known as rodlets. AFM investigation of the conidial surface allows us to evidence that RodA hydrophobins self-assemble into rodlets through bilayers. Within bilayers, hydrophilic domains of hydrophobins point inward, thus making a hydrophilic core, while hydrophobic domains point outward. AFM measurements reveal that several rodlet bilayers are present on the conidial surface thus showing that proteins self-assemble into a complex three-dimensional multilayer system. The self-assembly of RodA hydrophobins into rodlets results from attractive interactions between stacked β-sheets, which conduct to a final linear cross-β spine structure. A Monte Carlo simulation shows that anisotropic interactions are the main driving forces leading the hydrophobins to self-assemble into parallel rodlets, which are further structured in nanodomains. Taken together, these findings allow us to propose a mechanism, which conducts RodA hydrophobins to a highly ordered rodlet structure. The mechanism of hydrophobin assembly into rodlets offers new prospects for the development of more efficient strategies leading to disruption of rodlet formation allowing a rapid detection of the fungus by the immune system