Search Results (27)

Paraliobacillus zengyii CGMCC1.16464 (P. zengyii) is a novel antiviral probiotic candidate strain. To ensure its safety as a potential probiotic, a safety evaluation was conducted in this study. The safety and functional potential of P. zengyii were systematically assessed through genomic bioinformatics analysis, in vitro experiments, and acute oral toxicity tests in mice. Genomic analysis revealed that P. zengyii is rich in genes related to carbohydrate and amino acid metabolisms and carries genes encoding antimicrobial and antiviral agents (such as ectoine, type III polyketide synthase, and lasso peptides). It also expresses gastrointestinal tolerance-related proteins (ClpC, GroEL, and ClpP). Its resistance to polymyxins is an inherent trait with no risk of plasmid-mediated transfer. In vitro experiments confirmed that P. zengyii is somewhat tolerant to bile salts and acidic environments and does not exhibit hemolytic or gelatinase activity. Importantly, an acute oral toxicity test in mice revealed that after intervention with high, medium, or low doses, no significant abnormalities in the body weight, organ index, or tissue morphology of the mice were observed. In conclusion, P. zengyii exhibited good safety and probiotic potential in terms of genomic safety, metabolic function, and in vitro and in vivo toxicities, providing a theoretical basis for the development of novel functional probiotics. Full article

This study aimed to address the need for effective probiotics and antibacterial agents to combat American foulbrood disease in honeybees, caused by Paenibacillus larvae. In the context of declining honeybee populations due to pathogens, we isolated eight lactic acid bacteria (LAB) strains from honeybee larvae (Apis mellifera L.) and evaluated their probiotic potential and inhibitory effects against P. larvae. Methods included probiotic property assessments, such as acid and bile salt resistance, hydrophobicity, auto-aggregation, co-aggregation with P. larvae, antioxidant capacities, osmotolerance to 50% sucrose, and antibiotic susceptibility. Results indicated that the GL3 strain exhibited superior probiotic attributes and potent inhibitory effects on P. larvae. Whole-genome sequencing revealed GL3 to be an Enterococcus lactis strain with genetic features tailored to the honeybee larval gut environment. Pangenome analysis highlighted genetic diversity among E. lactis strains, while molecular docking analysis identified aborycin, a lasso peptide produced by GL3, as a promising inhibitor of bacterial cell wall synthesis. These findings suggested that GL3 was a promising probiotic candidate and antibacterial agent for honeybee health management, warranting further investigation into its in vivo efficacy and potential applications in beekeeping practices. Full article

Inflammatory bowel disease (IBD) is increasing among mammals around the world, and domestic dogs are no exception. There is no approved cure for canine IBD with limited treatment options. Novel probiotic bacteria discovery from free-ranging animals for the treatment of IBD in domestic pets can likely yield promising probiotic candidates. Consequently, the overall aim was to isolate bacteria from free-ranging animals that could potentially be utilized as novel probiotics. Two bacteria identified as unique Paenibacillus spp. strains by small ribosomal RNA (16S) gene sequencing were isolated from the gastrointestinal tract of a North American Gray Wolf (Canis lupus). The bacteria were typed as Gram-variable, and both were catalase/oxidase positive as well as sensitive to commonly used antibiotics. The bacteria digested complex carbohydrates and lipids by standard assays. The isolated bacteria also inhibited the growth of Staphylococcus aureus and Micrococcus luteus. The whole genome sequence (WGS) length of bacterial isolate ClWae17B was 6,939,193 bp, while ClWae19 was 7,032,512 bp, both similar in size to other Paenibacillus spp. The genomes of both bacteria encoded enzymes involved with the metabolism of complex starches and lipids, such as lyases and pectinases, along with encoding antimicrobials such as lanthipeptides, lasso peptides, and cyclic-lactone-autoinducers. No pernicious virulence genes were identified in the WGS of either bacterial isolate. Phylogenetically, the most closely related bacteria based on 16S gene sequences and WGS were P. taichungensis for ClWae17B and P. amylolyticus for ClWae19. WGS analyses and phenotypic assays supported the hypothesis that the isolates described constitute two novel candidate probiotic bacteria for potential use in dogs. Full article

Diabetes mellitus (DM) presents a critical global health challenge, characterized by persistent hyperglycemia and associated with substantial economic and health-related burdens. This study employs advanced machine-learning techniques to improve the prediction and classification of antidiabetic peptides, with a particular focus on differentiating those effective against T1DM from those targeting T2DM. We integrate feature selection with analysis methods, including logistic regression, support vector machines (SVM), and adaptive boosting (AdaBoost), to classify antidiabetic peptides based on key features. Feature selection through the Lasso-penalized method identifies critical peptide characteristics that significantly influence antidiabetic activity, thereby establishing a robust foundation for future peptide design. A comprehensive evaluation of logistic regression, SVM, and AdaBoost shows that AdaBoost consistently outperforms the other methods, making it the most effective approach for classifying antidiabetic peptides. This research underscores the potential of machine learning in the systematic evaluation of bioactive peptides, contributing to the advancement of peptide-based therapies for diabetes management. Full article

Genome mining and metabolomics have become valuable tools in natural products research to evaluate and identify potential new chemistry from bacteria. In the search for new compounds from the deep-sea organism, Pseudomonas sp. SST3, from the South Shetland Trough, Antarctica, a co-cultivation with a second deep-sea Pseudomonas zhaodongensis SST2, was undertaken to isolate pseudomonassin, a ribosomally synthesised and post-translationally modified peptide (RiPP) that belongs to a class of RiPP called lasso peptides. Pseudomonassin was identified using a genome-mining approach and isolated by means of mass spectrometric guided isolation. Extensive metabolomics analysis of the co-cultivation of Pseudomonas sp. SST3 and P. zhaodongensis SST2, Pseudomonas sp. SST3 and Escherichia coli, and P. zhaodongensis SST2 and E. coli were performed using principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA), which revealed potential new metabolites in the outlier regions of the co-cultivation, with other metabolites identified previously from other species of Pseudomonas. The sequence of pseudomonassin was completely deduced using high collision dissociation tandem mass spectrometry (HCD-MS/MS). Preliminary studies on its activity against the pathogenic P. aeruginosa and its biofilm formation have been assessed and produced a minimum inhibitory concentration (MIC) of 63 μg/mL and 28 μg/mL, respectively. Full article

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems. Full article

Myostatin, an important negative regulator of muscle mass, is a therapeutic target for muscle atrophic disorders such as muscular dystrophy. Thus, the inhibition of myostatin presents a strategy to treat these disorders. It has long been established that the myostatin prodomain is a strong inhibitor of the mature myostatin, and the minimum peptide of the prodomain—corresponding to the α₁-helix of its lasso-region—responsible for the inhibitory efficiency was defined and characterized as well. Here we show that the minimum peptide segment based on the growth differentiation factor 11 (GDF11), which we found to be more helical in its stand-alone solvated stfate than the similar segment of myostatin, is a promising new base scaffold for inhibitor design. The proposed inhibitory peptides in their solvated state and in complex with the mature myostatin were analyzed by in silico molecule modeling supplemented with the electronic circular dichroism spectroscopy measurements. We defined the Gaussian–Mahalanobis mean score to measure the fraction of dihedral angle-pairs close to the desired helical region of the Ramachandran-plot, carried out RING analysis of the peptide-protein interaction networks and characterized the internal motions of the complexes using our rigid-body segmentation protocol. We identified a variant—11m2—that is sufficiently ordered both in solvent and within the inhibitory complex, forms a high number of contacts with the binding-pocket and induces such changes in its internal dynamics that lead to a rigidified, permanently locked conformation that traps this peptide in the binding site. We also showed that the naturally evolved α₁-helix has been optimized to simultaneously fulfill two very different roles: to function as a strong binder as well as a good leaving group. It forms an outstanding number of non-covalent interactions with the mature core of myostatin and maintains the most ordered conformation within the complex, while it induces independent movement of the gate-keeper β-hairpin segment assisting the dissociation and also results in the least-ordered solvated form which provides extra stability for the dissociated state and discourages rebinding. Full article

Objective: We aimed to develop and validate a predictive machine learning (ML) model for cardiac surgery associated with acute kidney injury (CSA-AKI) based on a multicenter randomized control trial (RCT) and a Medical Information Mart for Intensive Care-IV (MIMIC-IV) dataset. Methods: This was a subanalysis from a completed RCT approved by the Ethics Committee of Fuwai Hospital in Beijing, China (NCT03782350). Data from Fuwai Hospital were randomly assigned, with 80% for the training dataset and 20% for the testing dataset. The data from three other centers were used for the external validation dataset. Furthermore, the MIMIC-IV dataset was also utilized to validate the performance of the predictive model. The area under the receiver operating characteristic curve (ROC-AUC), the precision-recall curve (PR-AUC), and the calibration brier score were applied to evaluate the performance of the traditional logistic regression (LR) and eleven ML algorithms. Additionally, the Shapley Additive Explanations (SHAP) interpreter was used to explain the potential risk factors for CSA-AKI. Result: A total of 6495 eligible patients undergoing cardiopulmonary bypass (CPB) were eventually included in this study, 2416 of whom were from Fuwai Hospital (Beijing), for model development, 562 from three other cardiac centers in China, and 3517 from the MIMICIV dataset, were used, respectively, for external validation. The CatBoostClassifier algorithms outperformed other models, with excellent discrimination and calibration performance for the development, as well as the MIMIC-IV, datasets. In addition, the CatBoostClassifier achieved ROC-AUCs of 0.85, 0.67, and 0.77 and brier scores of 0.14, 0.19, and 0.16 in the testing, external, and MIMIC-IV datasets, respectively. Moreover, the utmost important risk factor, the N-terminal brain sodium peptide (NT-proBNP), was confirmed by the LASSO method in the feature section process. Notably, the SHAP explainer identified that the preoperative blood urea nitrogen level, prothrombin time, serum creatinine level, total bilirubin level, and age were positively correlated with CSA-AKI; preoperative platelets level, systolic and diastolic blood pressure, albumin level, and body weight were negatively associated with CSA-AKI. Conclusions: The CatBoostClassifier algorithms outperformed other ML models in the discrimination and calibration of CSA-AKI prediction cardiac surgery with CPB, based on a multicenter RCT and MIMIC-IV dataset. Moreover, the preoperative NT-proBNP level was confirmed to be strongly related to CSA-AKI. Full article

Black band disease is a globally distributed and easily recognizable coral disease. Despite years of study, the etiology of this coral disease, which impacts dozens of stony coral species, is not completely understood. Although black band disease mats are predominantly composed of the cyanobacterial species Roseofilum reptotaenium, other filamentous cyanobacterial strains and bacterial heterotrophs are readily detected. Through chemical ecology and metagenomic sequencing, we uncovered cryptic strains of Roseofilum species from Siderastrea siderea corals that differ from those on other corals in the Caribbean and Pacific. Isolation of metabolites from Siderastrea-derived Roseofilum revealed the prevalence of unique forms of looekeyolides, distinct from previously characterized Roseofilum reptotaenium strains. In addition, comparative genomics of Roseofilum strains showed that only Siderastrea-based Roseofilum strains have the genetic capacity to produce lasso peptides, a family of compounds with diverse biological activity. All nine Roseofilum strains examined here shared the genetic capacity to produce looekeyolides and malyngamides, suggesting these compounds support the ecology of this genus. Similar biosynthetic gene clusters are not found in other cyanobacterial genera associated with black band disease, which may suggest that looekeyolides and malyngamides contribute to disease etiology through yet unknown mechanisms. Full article

Backgrounds: Advanced schistosomiasis is the late stage of schistosomiasis, seriously jeopardizing the quality of life or lifetime of infected people. This study aimed to develop a nomogram for predicting mortality of patients with advanced schistosomiasis japonica, taking Dongzhi County of China as a case study. Method: Data of patients with advanced schistosomiasis japonica were collected from Dongzhi Schistosomiasis Hospital from January 2019 to July 2022. Data of patients were randomly divided into a training set and validation set with a ratio of 7:3. Candidate variables, including survival outcomes, demographics, clinical features, laboratory examinations, and ultrasound examinations, were analyzed and selected by LASSO logistic regression for the nomogram. The performance of the nomogram was assessed by concordance index (C-index), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The calibration of the nomogram was evaluated by the calibration plots, while clinical benefit was evaluated by decision curve and clinical impact curve analysis. Results: A total of 628 patients were included in the final analysis. Atrophy of the right liver, creatinine, ascites level III, N-terminal procollagen III peptide, and high-density lipoprotein were selected as parameters for the nomogram model. The C-index, sensitivity, specificity, PPV, and NPV of the nomogram were 0.97 (95% [CI]: [0.95–0.99]), 0.78 (95% [CI]: [0.64–0.87]), 0.97 (95% [CI]: [0.94–0.98]), 0.78 (95% [CI]: [0.64–0.87]), 0.97 (95% [CI]: [0.94–0.98]) in the training set; and 0.98 (95% [CI]: [0.94–0.99]), 0.86 (95% [CI]: [0.64–0.96]), 0.97 (95% [CI]: [0.93–0.99]), 0.79 (95% [CI]: [0.57–0.92]), 0.98 (95% [CI]: [0.94–0.99]) in the validation set, respectively. The calibration curves showed that the model fitted well between the prediction and actual observation in both the training set and validation set. The decision and the clinical impact curves showed that the nomogram had good clinical use for discriminating patients with high risk of death. Conclusions: A nomogram was developed to predict prognosis of advanced schistosomiasis. It could guide clinical staff or policy makers to formulate intervention strategies or efficiently allocate resources against advanced schistosomiasis. Full article

The strain designated as AN120528^T was isolated from farmland soil in South Korea. This strain grows well on R2A medium at 28 °C. The cells are an off-white colour and have no hyphae. The phylogenetic analysis indicated that the strain is a member of the genus Shimazuella with a 98.11% similarity to Shimazuella alba KC615^T and a 97.05% similarity to S. kribbensis KCTC 9933^T, respectively. The strain AN120528^T shares common chemotaxonomic features with the other two type strains in the genus. It has MK-9 (H₄) and MK-10 (H₄) as its predominant menaquinones. The major fatty acids are iso-C_14:0, iso-C_15:0, anteiso-C_15:0 and iso-C_16:0. Diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), lipids (L), and aminolipids (AL) were identified as the major cellular polar lipids. Analysis of the peptidoglycan showed the presence of meso-diaminopimelic acid. Whole-genome sequencing revealed that the genome of the strain is approximately 3.3 Mbp in size. The strain showed a 77.5% average nucleotide identity (ANI) with S. alba KC615^T. The genomic DNA (gDNA) G + C content is 39.0%. Based on polyphasic taxonomy analysis, it is proposed that this strain, AN120528^T, represents a novel species in the genus Shimazuella, designated as Shimazuella soli sp. nov. The type stain is AN120528^T (=KCTC 39810^T = DSM 103571^T). Furthermore, shimazuellin I, a new 15-amino-acid peptide, was discovered in the AN120528^T through genome mining; it has the features of a lasso peptide, containing eight amino acids (-G-Q-G-G-S-N-N-D-) that form a macrolactam ring and seven amino acids (-D-G-W-Y-H-S-K-) that form a tail. Full article

Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. This metabolome-wide association study aimed to identify metabolomic markers for GWG. This longitudinal study included 39 Black and White pregnant women with a prepregnancy body mass index (BMI) of ≥ 25 kg/m². Untargeted metabolomic profiling was performed using fasting plasma samples collected at baseline (mean: 12.1 weeks) and 32 weeks of gestation. The associations of metabolites at each time point and changes between the two time points with GWG were examined by linear and least absolute shrinkage and selection operator (LASSO) regression analyses. Pearson correlations between the identified metabolites and cardiometabolic biomarkers were examined. Of the 769 annotated metabolites, 88 metabolites at 32 weeks were individually associated with GWG, with four (phosphatidylcholine (PC) 34:4, triacylglycerol (TAG) 52:6, arachidonic acid, isoleucine) jointly associated with GWG (area under the receiver operating characteristic curve (AUC) for excessive GWG: 0.80, 95% CI: 0.67, 0.93). No correlations were observed between the 88 metabolites and insulin, C-peptide, and high-sensitivity C-reactive protein at 32 weeks. Twelve metabolites at baseline (AUC for excessive GWG: 0.80, 95% CI: 0.62, 0.99) and three metabolite changes (AUC for excessive GWG: 0.73, 95% CI: 0.44, 1.00) were jointly associated with GWG. We identified novel metabolites in the first and third trimesters associated with GWG, which may shed light on the pathophysiology of GWG. Full article

Antimicrobial resistance has become a global problem in recent decades. A gradual reduction in drug discoveries has led to the current antimicrobial resistance crisis. Caves and other subsurface environments are underexplored thus far, and they represent indispensable ecological niches that could offer new molecules of interest to medicine and biotechnology. We explored Spanish show caves to test the bioactivity of the bacteria dwelling in the walls and ceilings, as well as airborne bacteria. We reported the isolation of two strains of the genus Crossiella, likely representing a new species, isolated from Altamira Cave, Spain. In vitro and in silico analyses showed the inhibition of pathogenic Gram-positive and Gram-negative bacteria, and fungi, as well as the taxonomical distance of both strains from their closest relative, Crossiella cryophila. The presence of an exclusive combination of gene clusters involved in the synthesis of lanthipeptides, lasso peptides, nonribosomal peptides and polyketides indicates that species of this genus could represent a source of new compounds. Overall, there is promising evidence for antimicrobial discovery in subterranean environments, which increases the possibility of identifying new bioactive molecules. Full article

The discovery of novel secondary metabolites is actively being pursued in new ecosystems. Sponge-associated bacteria have been in the limelight in recent years on account of their ability to produce bioactive compounds. In this study, heterotrophic bacteria associated with four sponge species were isolated, taxonomically identified, and subjected to screening for the production of bioactive entities against a panel of nine microorganisms, including Gram-positive and negative bacteria, as well as yeast and fungi. Of the 105 isolated strains, 66% were represented by Proteobacteria, 16% by Bacteriodetes, 7% by Actinobacteria, and 11% by Firmicutes. Bioactivity screening revealed that 40% of the total isolated strains showed antimicrobial activity against one or more of the target microorganisms tested. Further, active extracts from selective species were narrowed down by bioassay-guided fractionation and subsequently identified by HR-ESI-MS analyses to locate the active peaks. Presumably responsible compounds for the observed bioactivities were identified as pentadecenoic acid, oleic acid, and palmitoleic acid. One isolate, Qipengyuania pacifica NZ-96^T, based on 16S rRNA novelty, was subjected to comparative metabolic reconstruction analysis with its closest phylogenetic neighbors, revealing 79 unique functional roles in the novel isolate. In addition, genome mining of Qipengyuania pacifica NZ-96^T revealed three biosynthetic gene clusters responsible for the biosynthesis of terpene, beta lactone, lasso peptide, and hserlactone secondary metabolites. Our results demonstrate the ability to target the sponge microbiome as a potential source of novel microbial life with biotechnological potential. Full article

Lasso peptides are a subclass of ribosomally synthesized and post-translationally modified peptides (RiPPs) and feature the threaded, lariat knot-like topology. The basic post-translational modifications (PTMs) of lasso peptide contain two steps, including the leader peptide removal of the ribosome-derived linear precursor peptide by an ATP-dependent cysteine protease, and the macrolactam cyclization by an ATP-dependent macrolactam synthetase. Recently, advanced bioinformatic tools combined with genome mining have paved the way to uncover a rapidly growing number of lasso peptides as well as a series of PTMs other than the general class-defining processes. Despite abundant reviews focusing on lasso peptide discoveries, structures, properties, and physiological functionalities, few summaries concerned their unique PTMs. In this review, we summarized all the unique PTMs of lasso peptides uncovered to date, shedding light on the related investigations in the future. Full article