Induction of Isochromanones by Co-Cultivation of the Marine Fungus Cosmospora sp. and the Phytopathogen Magnaporthe oryzae

Microbial co-cultivation is a promising approach for the activation of biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. As part of our project aiming at the discovery of marine-derived fungal agrochemicals, we previously used four phytopathogens as model competitors in the co-cultivation of 21 marine fungal strains. Based on comparative untargeted metabolomics analyses and anti-phytopathogenic activities of the co-cultures, we selected the co-culture of marine Cosmospora sp. with the phytopathogen Magnaporthe oryzae for in-depth chemical studies. UPLC-MS/MS-based molecular networking (MN) of the co-culture extract revealed an enhanced diversity of compounds in several molecular families, including isochromanones, specifically induced in the co-culture. Large scale co-cultivation of Cosmospora sp. and M. oryzae resulted in the isolation of five isochromanones from the whole co-culture extract, namely the known soudanones A, E, D (1-3) and their two new derivatives, soudanones H-I (4-5), the known isochromans, pseudoanguillosporins A and B (6, 7), naphtho-γ-pyrones, cephalochromin and ustilaginoidin G (8, 9), and ergosterol (10). Their structures were established by NMR, HR-ESIMS, FT-IR, electronic circular dichroism (ECD) spectroscopy, polarimetry ([α]D), and Mosher’s ester reaction. Bioactivity assays revealed antimicrobial activity of compounds 2 and 3 against the phytopathogens M. oryzae and Phytophthora infestans, while pseudoanguillosporin A (6) showed the broadest and strongest anti-phytopathogenic activity against Pseudomonas syringae, Xanthomonas campestris, M. oryzae and P. infestans. This is the first study assessing the anti-phytopathogenic activities of soudanones

Glioma Associated Stem Cells (GASCs) Isolation and Culture.

Glioma Associated Stem Cells (GASCs) represent a population of nontumorigenic multipotent stem cells hosted in the microenvironment of human gliomas. In vitro, these cells are able, through the release of exosomes, to increase the biological aggressiveness of glioma-initiating cells. The clinical importance of this finding is supported by the strong prognostic value associated with the GASCs surface immunophenotype thus suggesting that this patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor strom

Analysis of LINE1 Retrotransposons in Huntington’s Disease

Transposable elements (TEs) are mobile genetic elements that made up about half the human genome. Among them, the autonomous non-LTR retrotransposon long interspersed nuclear element-1 (L1) is the only currently active TE in mammals and covers about 17% of the mammalian genome. L1s exert their function as structural elements in the genome, as transcribed RNAs to influence chromatin structure and as retrotransposed elements to shape genomic variation in somatic cells. L1s activity has been shown altered in several diseases of the nervous system. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expansion of a CAG repeat in the HTT gene which leads to a gradual loss of neurons most prominently in the striatum and, to a lesser extent, in cortical brain regions. The length of the expanded CAG tract is related to age at disease onset, with longer repeats leading to earlier onset. Here we carried out bioinformatic analysis of public RNA-seq data of a panel of HD mouse models showing that a decrease of L1 RNA expression recapitulates two hallmarks of the disease: it correlates to CAG repeat length and it occurs in the striatum, the site of neurodegeneration. Results were then experimentally validated in HttQ111 knock-in mice. The expression of L1-encoded proteins was independent from L1 RNA levels and differentially regulated in time and tissues. The pattern of expression L1 RNAs in human HD post-mortem brains showed similarity to mouse models of the disease. This work suggests the need for further study of L1s in HD and adds support to the current hypothesis that dysregulation of TEs may be involved in neurodegenerative diseases

Emerging treatment options for multi-drug-resistant bacterial infections

Antimicrobial resistance (AMR) remains one of the top public health issues of global concern. Among the most important strategies for AMR control there is the correct and appropriate use of antibiotics, including those available for the treatment of AMR pathogens. In this article, after briefly reviewing the most important and clinically relevant multi-drug-resistant bacteria and their main resistance mechanisms, we describe the emerging antimicrobial options for both MDR Gram-positive cocci and Gram-negative bacilli, including recently marketed agents, molecules just approved or under evaluation and rediscovered older antibiotics that have regained importance due to their antimicrobial spectrum. Specifically, emerging options for Gram-positive cocci we reviewed include ceftaroline, ceftobiprole, tedizolid, dalbavancin, and fosfomycin. Emerging treatment options for Gram-negative bacilli we considered comprise ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, minocycline, fosfomycin, eravacycline, plazomicin, and cefiderocol. An exciting scenario is opening today with the long awaited growing availability of novel molecules for the treatment of AMR bacteria. Knowledge of mechanisms of action and resistance patterns allows physicians to increasingly drive antimicrobial treatment towards a precision medicine approach. Strict adherence to antimicrobial stewardship practices will allow us to preserve the emerging antimicrobials for our future

Sterol composition of three marine sponge species from the genus Cinachyrella

The hitherto undescribed sterol composition of three marine sponge species belonging to the genus #Cynachyrella are reported : #C. alloclada and #C. kukenthali from the Senegalese coast, at two different depths, and C. aff. #schultezei from the lagoon of Nouméa, New Caledonia. (D'après résumé d'auteur