Invasive Infections Due to Trichosporon: Species Distribution, Genotyping, and Antifungal Susceptibilities from a Multicenter Study in China.

A total of 133 clinical Trichosporon isolates were collected in the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program in 2009 to 2016. Accurate identification was performed by sequencing of the intergenic spacer 1 (IGS1) region. Among these isolates, Trichosporon asahii (108 isolates [81.2%]) was the leading species, followed by Trichosporon dermatis (7 isolates [5.3%]), Trichosporon asteroides (5 isolates [3.8%]), Trichosporon inkin (5 isolates [3.8%]), Trichosporon dohaense (3 isolates [2.3%]), and 1 isolate (0.7%) each of Trichosporon faecale, Trichosporon jirovecii, Trichosporon mucoides, Trichosporon coremiiforme, and Trichosporon montevideense Both the Vitek mass spectrometry (MS) (bioMérieux, Marcy l'Etoile, France) and Bruker Biotyper MS (Bruker Daltonics GmbH, Germany) platforms gave high levels (>97.5%) of correct identification when the species were present in the database. The geometric mean (GM) of amphotericin B MICs for T. asahii was 2-fold higher than that for non-asahii Trichosporon High fluconazole MICs (≥8 µg/ml) were observed for 25% of T. asahii isolates (27/108 isolates) and 16% of non-asahii Trichosporon (4/25 isolates) isolates. Itraconazole MICs were ≤0.5 µg/ml for 89.5% of the isolates. Voriconazole was the most potent antifungal agent in vitro, with a GM of 0.09 µg/ml. Genotyping of the isolates using IGS1 sequence alignment revealed that genotype 1 was most common (41.7%), followed by genotype 4 (31.5%), genotype 3 (23.1%), genotype 5 (0.9%), genotype 6 (0.9%), and genotype 7 (1.8%). Our data on species distribution, genotypes, and antifungal susceptibilities may contribute to a better understanding of the epidemiology of invasive Trichosporon infections throughout China.

From phosphorylation to phenotype - Recent key findings on kinase regulation, downstream signaling and disease surrounding the receptor tyrosine kinase MuSK.

Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development. MuSK acts via several distinct pathways and is responsible for pre- and postsynaptic differentiation. MuSK is unique among receptor tyrosine kinases as activation and signaling are particularly tightly regulated. Initiation of kinase activity requires Agrin, a heparan sulphate proteoglycan derived from motor neurons, the low-density lipoprotein receptor-related protein-4 (Lrp4) and the intracellular adaptor protein Dok-7. There is a great knowledge gap between MuSK activation and downstream signaling. Recent studies using omics techniques have addressed this knowledge gap, thereby greatly contributing to a better understanding of MuSK signaling. Impaired MuSK signaling causes severe muscle weakness as described in congenital myasthenic syndromes or myasthenia gravis but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling. We further highlight latest break-throughs in understanding and treatment of MuSK-related disorders and discuss the role of MuSK in non-muscle tissue.

Internalization of Muscle-Specific Kinase Is Increased by Agrin and Independent of Kinase-Activity, Lrp4 and Dynamin.

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase absolutely required for neuromuscular junction formation. MuSK is activated by binding of motor neuron-derived Agrin to low-density lipoprotein receptor related protein 4 (Lrp4), which forms a complex with MuSK. MuSK activation and downstream signaling are critical events during the development of the neuromuscular junction. Receptor tyrosine kinases are commonly internalized upon ligand binding and crosstalk between endocytosis and signaling has been implicated. To extend our knowledge about endocytosis of synaptic proteins and its role during postsynaptic differentiation at the neuromuscular junction, we studied the stability and internalization of Lrp4, MuSK and acetylcholine receptors (AChRs) in response to Agrin. We provide evidence that MuSK but not Lrp4 internalization is increased by Agrin stimulation. MuSK kinase-activity is not sufficient to induce MuSK internalization and the absence of Lrp4 has no effect on MuSK endocytosis. Moreover, MuSK internalization and signaling are unaffected by the inhibition of Dynamin suggesting that MuSK endocytosis uses a non-conventional pathway and is not required for MuSK-dependent downstream signaling.

Transcriptome-wide expression profiling of Sporothrix schenckii yeast and mycelial forms and the establishment of the Sporothrix Genome DataBase.

Sporothrix schenckii is a dimorphic fungus existing as mould in the environment and as yeast in the host. The morphological shift between mycelial/yeast phases is crucial for its virulence, but the transcriptional networks implicated in dimorphic transition are still not fully understood. Here, we report the global transcriptomic differences occurring between mould and yeast phases of S. schenckii, including changes in gene expression profiles associated with these distinct cellular phenotypes. Moreover, we also propose a new genome annotation, which reveals a more complex transcriptional architecture than previously assumed. Using RNA-seq, we identified a total of 17 307 genes, of which 11 217 were classified as protein-encoding genes, whereas 6090 were designated as non-coding RNAs (ncRNAs). Approximately ~71 % of all annotated genes were found to overlap and the different-strand overlapping type was the most common. Gene expression analysis revealed that 8795 genes were differentially regulated among yeast and mould forms. Differential gene expression was also observed for antisense ncRNAs overlapping neighbouring protein-encoding genes. The release of transcriptome-wide data and the establishment of the Sporothrix Genome DataBase (http://sporothrixgenomedatabase.unime.it) represent an important milestone for Sporothrix research, because they provide a strong basis for future studies on the molecular pathways involved in numerous biological processes.

Arthrographis curvata and Rhodosporidium babjevae as New Potential Fungal Lipase Producers for Biotechnological Applications

Abstract Fungi have always attracted a lot of attention as they are able to produce a vast repertoire of enzymes that find a broad spectrum of uses in biotechnological and industrial fields. Undoubtedly, one of the most promising biocatalysts is the lipase, which has been widely used for the biotransformation of a number of commercial products due to its high stability, high catalytic efficiency, versatility and selectivity, making it one of the most attractive and best-studied enzymes. In this study we report the isolation and molecular identification of new lipase-producing fungi from different environmental samples from Morocco. The production and activity of extracellular lipases, at different parameters, was evaluated using the Rhodamine B agar, submerged fermentation and biochemical methods. Two fungal strains Arthrographis curvata and Rhodosporidium babjevae, were isolated and found to produce large amounts of lipases. The optimal activity of the extracellular lipase was detected at 40°C and pH 9.0 for A. curvata and at 40 °C and pH 8.0 for R. babjevae. This study add new information at the growing list of fungal species producing lipases with improved physicochemical proprieties which could constitute a new line of research for further studies and to be exploited for industrial or bioremediation purposes.