The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms’ genomes, the development of more representative disease models and improvement of techniques, technologies, and computation applied to biology are advances that will foster drug discovery in upcoming years. In this paper, several aspects of current methodologies for drug discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm and antiquorum sensing, anticancer and neuroprotectors are considered. For drug discovery, two different complementary approaches can be applied: classical pharmacology, also known as phenotypic drug discovery, which is the historical basis of drug discovery, and reverse pharmacology, also designated target-based drug discovery. Screening methods based on phenotypic drug discovery have been used to discover new natural products mainly from terrestrial origin. Examples of the discovery of marine natural products are provided. A section on future trends provides a comprehensive overview on recent advances that will foster the pharmaceutical industry.
The gastrointestinal microbiota plays a critical role on host health and metabolism. This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production. A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants. The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish. The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients. Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP. By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential. By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics. This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
The Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM) classification correlates with histological assessment of gastric intestinal metaplasia and enables stratification of gastric cancer risk. We developed and evaluated an artificial intelligence (AI) approach for EGGIM estimation. Two datasets (A and B) with 1280 narrow-band imaging images were used for per-image analysis. Still images with manually selected patches of 224 × 224 pixels, annotated by experts, were used. Dataset A was retrospectively collected from clinical routine; Dataset B (used for per-patient analysis) was prospectively collected and included 65 fully documented patients. To mimic clinical practice, a deep neural network classified image patches into three EGGIM classes (0, 1, 2) and calculated the total per-patient EGGIM score (0–10). On per-image analysis, an accuracy of 87% (95%CI 71%–100%) was obtained. Per-patient EGGIM estimation had an average error of 1.15 (out of 10) and showed 88% (95%CI 80%–96%) accurate clinical decisions for surveillance (EGGIM ≥5), with 85% (95%CI 75%–94%) specificity, no false negatives, and positive and negative predictive values of 62% (95%CI 32%–92%) and 100% (95%CI 100%–100%), respectively. EGGIM was estimated with high accuracy using AI tools in endoscopic image analyses. Automated assessment of EGGIM may provide a greener strategy for gastric cancer risk stratification, prospective studies, and interventional trials.
A novel micro-organism designated AS10Twas isolated from dry salt collected from Aveiro saltern in the north of Portugal. Cells were Gram-stain-positive, non-motile, non-endospore-forming, rod-shaped and aerobic. Strain AS10Twas characterized by long filaments of rod-shaped cells, presenting also coccoid cellular forms at the end of the filaments, unveiling some pleomorphism. Rod-shaped cells varied from 0.3 to 0.6 µm wide and from 0.6 to 2 µm long. Growth of AS10Toccurred at 15–40 °C (optimum, 20–30 °C), 0–10% (w/v) NaCl (optimum, 2%) and pH 4.5–11.0 (optimum, pH 8.0–11.0). The peptidoglycan type was A1ϒ-type with 3-hydroxy-diaminopimelic acid. The major fatty acids were C16:0, iso-C14:0, C17:0and C14:0. The major respiratory quinone was MK-9(H4). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain AS10Twas similar to actinobacterial members of the classNitriliruptoria, withNitriliruptor alkaliphilusANL-iso2Tbeing the closest relative the species with a sequence pairwise similarity of 91.21%. Average nucleotide identity, average amino acid identity andin silicoDNA–DNA hybridization values between strain AS10TandN. alkaliphilusANL-iso2Twere 71.34, 53.57 and 18.90%, respectively. The genome DNA G+C content of AS10Twas 71.8 mol%. Based on genomic, phylogenetic, phenotypic and chemotaxonomic studies, we describe a new species of a novel genus represented by strain AS10T(=LMG 31937T=CECT 30148T) for which we propose the nameSalsipaludibacter albusgen. nov., sp. nov. We also propose that this organism represents a new family namedSalsipaludibacteraceaefam. nov. of a novel order namedSalsipaludibacteralesord. nov.
Background: The high salt concentration is the major factor limiting microbial growth at salterns, along with solar radiation, temperature, and pH. These environmental factors play key roles in the acquisition of unique genetic adaptations for the survival of microorganisms in salterns, which can result in the production of interesting secondary metabolites. The main goal of the present work was to isolate and compare the culturable microbiota from two geographically distant salterns in Portugal and access their biotechnological potential. Methods: Culturomics approaches using different culture media were applied for microbial isolation. All isolates were identified either by 16S rRNA or ITS genes sequencing, and their biotechonological potential was assessed by PCR. Results: Overall, 154 microbial isolates were recovered that were phylogenetically assigned to 45 taxa from 9 different phyla. From these, 26 isolates may represent putative new taxa. The predominant genera obtained were Penicillium (41 isolates, 26.6%), Streptomyces (13 isolates, 8.4%) and Sinomicrobium (11 isolates, 7.1%). Moreover, the polyketide synthase I gene was present in 64 isolates, the nonribosomal peptide synthethase gene in 16 isolates, and both genes in 23 isolates. Conclusions: This study adds up valuable knowledge on the culturable microbiota of Portuguese salterns and on its potential for production of secondary metabolites. In the long run, this study provides a widely diverse microbial collection for future works. Data public repository: All DNA sequences were deposited in the GenBank database at National Centre for Biotechnology Information (NCBI) web platform under accession numbers OK169439-OK169485, OK216020-OK216124, OK287059 and OK326927.