27 research outputs found

    Rasamsonia argillacea species complex: taxonomy, pathogenesis and clinical relevance.

    Get PDF
    Since 2010, colonizations/infections by Rasamsonia argillacea species complex, previously known as Geosmithia argillacea, have been regularly reported in literature. We reviewed all available cases focusing on pathogenesis and clinical relevance. The number of cases may be underestimated, as these fungi are frequently misidentified as Penicillium or Paecilomyces species. Major underlying conditions that predispose for infections by the R. argillacea species complex include cystic fibrosis (CF) and chronic granulomatous disease (CGD). While the pathogenic role of the colonization of CF lungs is still under debate, these molds are the causative agent of pneumonia and/or invasive infections in CGD patients. Given their thermotolerance and their resistance to various antifungals, especially the azole drugs, a special attention should be paid to the chronic colonization of the airways by these fungi in CF and CGD patients

    Identification and Characterization of Mediators of Fluconazole Tolerance in Candida albicans.

    Get PDF
    Candida albicans is an important human pathogen and a major concern in intensive care units around the world. C. albicans infections are associated with a high mortality despite the use of antifungal treatments. One of the causes of therapeutic failures is the acquisition of antifungal resistance by mutations in the C. albicans genome. Fluconazole (FLC) is one of the most widely used antifungal and mechanisms of FLC resistance occurring by mutations have been extensively investigated. However, some clinical isolates are known to be able to survive at high FLC concentrations without acquiring resistance mutations, a phenotype known as tolerance. Mechanisms behind FLC tolerance are not well studied, mainly due to the lack of a proper way to identify and quantify tolerance in clinical isolates. We proposed here culture conditions to investigate FLC tolerance as well as an easy and efficient method to identity and quantify tolerance to FLC. The screening of C. albicans strain collections revealed that FLC tolerance is pH- and strain-dependent, suggesting the involvement of multiple mechanisms. Here, we addressed the identification of FLC tolerance mediators in C. albicans by an overexpression strategy focusing on 572 C. albicans genes. This strategy led to the identification of two transcription factors, CRZ1 and GZF3. CRZ1 is a C2H2-type transcription factor that is part of the calcineurin-dependent pathway in C. albicans, while GZF3 is a GATA-type transcription factor of unknown function in C. albicans. Overexpression of each gene resulted in an increase of FLC tolerance, however, only the deletion of CRZ1 in clinical FLC-tolerant strains consistently decreased their FLC tolerance. Transcription profiling of clinical isolates with variable levels of FLC tolerance confirmed a calcineurin-dependent signature in these isolates when exposed to FLC

    Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and accurate identification of Pseudallescheria/Scedosporium species

    Get PDF
    An increasing number of infections due to Pseudallescheria/Scedosporium species has been reported during the past decades, both in immunocompromised and immunocompetent patients. Additionally, these fungi are now recognized worldwide as common agents of fungal colonization of the airways in cystic fibrosis patients, which represents a risk factor for disseminated infections after lung transplantation. Currently six species are described within the Pseudallescheria/Scedosporium genus, including Scedosporium prolificans and species of the Pseudallescheria/Scedosporium apiospermum complex (i.e. S. apiospermum sensu stricto, Pseudallescheria boydii, Scedosporium aurantiacum, Pseudallescheria minutispora and Scedosporium dehoogii). Precise identification of clinical isolates at the species level is required because these species differ in their antifungal drug susceptibility patterns. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/mass spectrometry (MS) is a powerful tool to rapidly identify moulds at the species level. We investigated the potential of this technology to discriminate Pseudallescheria/Scedosporium species. Forty-seven reference strains were used to build a reference database library. Profiles from 3-, 5- and 7-day-old cultures of each reference strain were analysed to identify species-specific discriminating profiles. The database was tested for accuracy using a set of 64 clinical or environmental isolates previously identified by multilocus sequencing. All isolates were unequivocally identified at the species level by MALDI-TOF/MS. Our results, obtained using a simple protocol, without prior protein extraction or standardization of the culture, demonstrate that MALDI-TOF/MS is a powerful tool for rapid identification of Pseudallescheria/Scedosporium species that cannot be currently identified by morphological examination in the clinical setting

    Drug trials with

    No full text
    The filaria Monanema martini, with skin-dwelling microfilariae, which induces onchocerca-like lesions, is well appropriate for drug trials.These are performed together with a histopathological study of side-effects on the murid host

    Ivermectin and moxidectin in two filarial systems : resistance of Monanema martini; inhibition of Litomosoides sigmodontis insemination

    No full text
    Effects of ivermectin and moxidectin were compared on two filarial species : #Monanema martini which presents dermal microfilariae and induces #Onchocerca-like lesions in its natural murid host #Lemniscomys striatus, and #Litomosoides sigmodontis (=#L. carinii). #M. martini microfilariae showed an unusual resistance to ivermectin, in vitro and in vivo ; moxidectin was no more efficient. However, the two drugs used at high concentrations deeply altered the uterine embryogenesis, but had no lethal effect on adult filariae. #L. sigmodontis blood microfilariae showed a great susceptibility to moxidectin, similar to that previously described for ivermectin. The two drugs also induced a long term effect because they inhibited the insemination of the female filariae. This result reinforces the observations made by other authors on the human parasite, #Onchocerca volvulus. (Résumé d'auteur
    corecore