.
OBJECTIVES:Bacillus cereus sensu lato (s.l.) or B. cereus group increasingly causes severe infections in preterm neonates. However, species-level identification and virulence characterization remain limited. This study aimed to identify B. cereus group species responsible for invasive infections in preterm neonates and to correlate genomic virulence profiles with clinical outcomes. METHODS:We conducted a retrospective, multicentre study across 13 French hospitals (2010-2021), including 40 B. cereus group isolates from blood or cerebrospinal fluid of preterm neonates with invasive infections. Clinical data were extracted from patient records. Whole-genome sequencing (WGS) (Illumina and Oxford Nanopore) with hybrid assemblies enabled species identification using digital DNA-DNA hybridization and average nucleotide identity. Virulence genes were screened against a curated database of 65 virulence genes, and associations with clinical outcomes were analysed. RESULTS:Forty isolates were analysed, 42.5% (17 of 40) of patients developed septic shock, and 37.5% (15 of 40), died, usually after rapid clinical deterioration. WGS identified seven species, predominantly Bacillus paranthracis (47.5%, 19 of 40) and B. cereus sensu stricto (20%, 8 of 40). Virulence gene content varied by species. The presence of hblCDAB (60%, 9 of 15), nprB (46.5%, 7 of 15), asbABCDEF (80%, 12 of 15), and essC-cereus/esxA (66.7%, 10 of 15) genes correlated with mortality (p 0.00015, 0.002, 0.0027, and 0.02, respectively). B. cereus sensu stricto carried more virulence determinants and was associated with higher mortality than B. paranthracis and other species, at day 7 (p 0.05) and at day 28 (p 0.0065). The cesH gene (60%, 15 of 25) is significantly associated with survival (p 0.007), particularly with B. paranthacis, the predominant species in our cohort. CONCLUSIONS:Invasive B. cereus group infections in preterm neonates are associated with high mortality, particularly in cases due to B. cereus sensu stricto. WGS enables precise species identification and virulence profiling, which are essential insights for diagnostic refinement, outbreak control, and risk stratification in neonatal intensive care settings.
Abstract Octocorals are vital components of tropical, temperate, and cold-water benthic marine ecosystems. Their associated microbiomes, comprising microeukaryotes, prokaryotes, and viruses, are increasingly recognised as central to host health, nutrient cycling, and chemical defence. Metagenomics and amplicon sequencing have uncovered taxonomic and functional complexity within these microbial communities, revealing patterns of host specificity and health status, along with seasonality and geographic structuring. However, anthropogenic stressors, particularly those associated with global climate change, exert intense pressure on coral-dominated ecosystems, leading to complex and poorly understood local and regional patterns of octocoral expansion and mortality. Microbial interactions may be a main driver of these contrasting outcomes by mediating the ecological resilience of octocorals to environmental stress. We synthesise the current state of research on the diversity, organisation, and function of the octocoral microbiome, and identify critical knowledge gaps on octocoral holobionts relative to scleractinian corals. Our meta-analysis of 79 publicly available bacterial genomes from octocorals reveals group-specific specialisation in denitrification and nitrate assimilation, along with widespread capacities for essential amino acid, cofactor, and vitamin production, suggesting important contributions to nutrient cycling in the holobiont. While sampling efforts between cultured and uncultured lineages are even, our genomic survey reveals strong sampling bias toward the Atlantic Ocean, temperate gorgonians, and healthy host states, whereas bacterial genomes representing the pathobiome, tropical and/or deep-sea regions, and other octocoral taxa remain underrepresented. Accordingly, we propose future research directions to advance understanding of octocoral microbiome ecology and its role in the resilience of tropical, temperate and cold-water coral reefs.
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, with deletions within the exon 45-55 hotspot being the most common. Despite advances in antisense oligonucleotide (ASO)-mediated exon skipping, therapeutic efficacy remains limited by suboptimal transcript availability and delivery barriers. We investigated whether histone deacetylase inhibitors (HDACis), particularly givinostat, can enhance the efficacy of an exon 51-targeting ASO in the clinically relevant mdx52 mouse model. For the first time, we identified a pronounced 5'-3' DMD transcript imbalance associated with exon 52 deletion, contrasting with the classical mdx model and potentially compromising ASO effectiveness. In human DMD myoblasts carrying an exon 52 deletion, givinostat significantly improved exon skipping and dystrophin restoration. In vivo, givinostat and ASO co-treatment resulted in a modest but significant increase in dystrophin levels compared to ASO alone (1.3-fold), along with reduced muscle fibrosis, improved fiber morphology, and better extracellular matrix organization. Notably, treated mice showed improved muscle function, as evidenced by a significant reduction in force loss after eccentric contractions, a clinically meaningful outcome. Although the precise molecular mechanisms underlying these effects remain to be fully elucidated, these findings support the therapeutic potential of combining givinostat with ASOs to enhance dystrophin restoration and muscle preservation in DMD.
Carbon (C) and nitrogen (N) are essential nutrients for coral–Symbiodiniaceae associations, yet global change can disrupt C and N acquisition by corals, affecting their resilience under stress. We investigated how two octocorals (Sarcophyton glaucum, Lobophytum sp.) and two hexacorals (Stylophora pistillata, Turbinaria reniformis) assimilate nitrogen from three 15N-labelled sources—dissolved free amino acids (DFAAs), Synechococcus (picoplankton), and Artemia salina nauplii (microplankton)—supplied at 1 µM N, under control (26 °C) and heat stress (30 °C) conditions. Corals were also incubated with natural pico-nanoplankton assemblages, with concentrations measured via flow cytometry. In addition, we measured the rates of photosynthesis and respiration, to estimate the relative contribution of autotrophy to the corals’ respiratory needs. Across all species, Synechococcus was the most efficiently assimilated N source, with uptake increasing under heat stress. Estimates of heterotrophic carbon assimilation (using C:N ratio) coupled with respiratory measurements showed that Synechococcus can provide 30–70
