The pathology of sponge orange band disease affecting the Caribbean barrel sponge Xestospongia muta

The aim of this study was to examine sponge orange band (SOB) disease affecting the prominent Caribbean sponge Xestospongia muta. Scanning and transmission electron microscopy revealed that SOB is accompanied by the massive destruction of the pinacoderm. Chlorophyll a content and the main secondary metabolites, tetrahydrofurans, characteristic of X. muta, were significantly lower in bleached than in healthy tissues. Denaturing gradient gel electrophoresis using cyanobacteria-specific 16S rRNA gene primers revealed a distinct shift from the Synechococcus/Prochlorococcus clade of sponge symbionts towards several clades of unspecific cyanobacteria, including lineages associated with coral disease (i.e. Leptolyngbya sp.). Underwater infection experiments were conducted by transplanting bleached cores into healthy individuals, but revealed no signs of SOB development. This study provided no evidence for the involvement of a specific microbial pathogen as an etiologic agent of disease; hence, the cause of SOB disease in X. muta remains unidentified

Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta)

Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H]− equivalent to C64H104O33 and the putatively found active metabolite at m/z 1283.58 [M + formic-H]− corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosomal activity of 98.9% inhibition at 20 µM

Nature as a treasure trove of potential anti-SARS-CoV drug leads:a structural/mechanistic rationale

The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reported in vitro efficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (M(pro)). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates, viz. acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future

A New Bioactive Compound From the Marine Sponge-Derived Streptomyces sp. SBT348 Inhibits Staphylococcal Growth and Biofilm Formation

Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 μg/ml) and biofilm formation (sub-MIC range: 1.95–<31.25 μg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs

An Enrichment of CRISPR and Other Defense-Related Features in Marine Sponge-Associated Microbial Metagenomes

Many marine sponges are populated by dense and taxonomically diverse microbial consortia. We employed a metagenomics approach to unravel the differences in the functional gene repertoire among three Mediterranean sponge species, Petrosia ficiformis, Sarcotragus foetidus, Aplysina aerophoba and seawater. Different signatures were observed between sponge and seawater metagenomes with regard to microbial community composition, GC content, and estimated bacterial genome size. Our analysis showed further a pronounced repertoire for defense systems in sponge metagenomes. Specifically, clustered regularly interspaced short palindromic repeats, restriction modification, DNA phosphorothioation and phage growth limitation systems were enriched in sponge metagenomes. These data suggest that defense is an important functional trait for an existence within sponges that requires mechanisms to defend against foreign DNA from microorganisms and viruses. This study contributes to an understanding of the evolutionary arms race between viruses/phages and bacterial genomes and it sheds light on the bacterial defenses that have evolved in the context of the sponge holobiont

Discovery and structural assignment of (S)-sydosine from amphipod-derived Aspergillus sydowii MBC15-11F through HRMS, advanced Mosher, and molecular modelling analyses

AimsThis study aims to prioritize fungal strains recovered from under-explored habitats that produce new metabolites. HRMS dereplication is used to avoid structure redundancy, and molecular modelling is used to assign absolute configuration.Methods and resultsMBC15-11F was isolated from an amphipod and identified using ITS, 28S, and β-tubulin phylogeny as Aspergillus sydowii. Chemical profiling using taxonomic-based dereplication identified structurally diverse metabolites, including unreported ones. Large-scale fermentation led to the discovery of a new N-acyl adenosine derivative: (S)-sydosine (1) which was elucidated by NMR and HRESIMS analyses. Two known compounds were also identified as predicted by the initial dereplication process. Due to scarcity of 1, molecular modelling was used to assign its absolute configuration without hydrolysis, and is supported by advanced Mosher derivatization. When the isolated compounds were assessed against a panel of bacterial pathogens, only phenamide (3) showed anti-Staphylococcus aureus activity.ConclusionFermentation of A. sydowii yielded a new (S)-sydosine and known metabolites as predicted by HRESIMS-aided dereplication. Molecular modelling prediction of the absolute configuration of 1 agreed with advanced Mosher analysis

Wound healing and antioxidant properties of <i>Launaea procumbens</i> supported by metabolomic profiling and molecular docking

Wounds adversely affect people’s quality of life and have psychological, social, and economic impacts. Herbal remedies of Launaea procumbens (LP) are used to treat wounds. In an excision wound model, topical application of LP significantly promoted wound closure (on day 14, LP-treated animals had the highest percentages of wound closure in comparison with the other groups, as the wound was entirely closed with a closure percentage of 100%, p < 0.05). Histological analysis revealed a considerable rise in the number of fibroblasts, the amount of collagen, and its cross-linking in LP-treated wounds. Gene expression patterns showed significant elevation of TGF-β levels (2.1-fold change after 7 days treatment and 2.7-fold change in 14 days treatment) and downregulation of the inflammatory TNF-α and IL-1β levels in LP-treated wounds. Regarding in vitro antioxidant activity, LP extract significantly diminished the formation of H(2)O(2) radical (IC(50) = 171.6 μg/mL) and scavenged the superoxide radical (IC(50) of 286.7 µg/mL), indicating antioxidant potential in a dose-dependent manner. Dereplication of the secondary metabolites using LC-HRMS resulted in the annotation of 16 metabolites. The identified compounds were docked against important wound-healing targets, including vascular endothelial growth factor (VEGF), collagen α-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β). Among dereplicated compounds, luteolin 8-C-glucoside (orientin) demonstrated binding potential to four investigated targets (VEGF, interleukin 1β, TNF-α, and collagen α-1). To conclude, Launaea procumbens extract could be regarded as a promising topical therapy to promote wound healing in excisional wounds, and luteolin 8-C-glucoside (orientin), one of its constituents, is a potential wound-healing drug lead

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Williamsia herbipolensis sp. nov., isolated from the phyllosphere of Arabidopsis thaliana

A Gram-stain-positive, non-endospore-forming actinobacterium (ARP1T) was isolated from the phyllosphere of Arabidopsis thaliana. On the basis of 16S rRNA gene sequence phylogeny strain ARP1T was placed into the genus Williamsia and the closest related species were Williamsia phyllosphaerae (98.5 % 16S rRNA gene sequence similarity), Williamsia deligens (98.5 %), Williamsia maris (98.3 %) and Williamsia serinedens (98.2 %). Genome-based comparison indicated a clear distinction to the type strains of those species with pairwise average nucleotide identities (ANI) between 76.4–78.4 %. The quinone system of strain ARP1T consisted predominantly of menaquinones MK-9(H2), MK-7(H2) and MK-8(H2), and the polar lipid profile contained the major compound diphosphatidylglycerol, and moderate amounts of phosphatidylethanolamine, phosphatidylglycerol and numerous unidentified lipids. Mycolic acids were present. These chemotaxonomic traits and the major fatty acids, which were C16 : 1ω7c, C16 : 0, C18 : 0, C18 : 1ω9c and tuberculostearic acid supported the affiliation of strain ARP1T to the genus Williamsia . Genotypic, physiological and biochemical testing revealed clear differences of strain ARP1T to the most closely related species of the genus Williamsia . Therefore strain ARP1T represents a novel species of this genus, for which the name Williamsia herbipolensis sp. nov. is proposed. The type strain is ARP1T (=DSM 46872T=LMG 28679T)