Draft Genome Sequence of Micromonospora sp. Strain MW-13, a Bacterial Strain with Antibacterial Properties and Plant Growth Promotion Potential Isolated from the Rhizosphere of Wheat in Iran.

Jahanshah G, Miess H, Busche T, et al. Draft Genome Sequence of Micromonospora sp. Strain MW-13, a Bacterial Strain with Antibacterial Properties and Plant Growth Promotion Potential Isolated from the Rhizosphere of Wheat in Iran. Microbiology resource announcements. 2019;8(2): e01375-18

Deciphering the Transcriptional Response Mediated by the Redox-Sensing System HbpS-SenS-SenR from Streptomycetes

Busche T, Winkler A, Wedderhoff I, Rückert C, Kalinowski J, Lucana DO de O. Deciphering the Transcriptional Response Mediated by the Redox-Sensing System HbpS-SenS-SenR from Streptomycetes. PLOS ONE. 2016;11(8): e0159873.The secreted protein HbpS, the membrane-embedded sensor kinase SenS and the cytoplasmic response regulator SenR from streptomycetes have been shown to form a novel type of signaling pathway. Based on structural biology as well as different biochemical and biophysical approaches, redox stress-based post-translational modifications in the three proteins were shown to modulate the activity of this signaling pathway. In this study, we show that the homologous system, named here HbpSc-SenSc-SenRc, from the model species Streptomyces coelicolor A3(2) provides this bacterium with an efficient defense mechanism under conditions of oxidative stress. Comparative analyses of the transcriptomes of the Streptomyces coelicolor A3(2) wild-type and the generated hbpSc-senSc-senRc mutant under native and oxidative-stressing conditions allowed to identify differentially expressed genes, whose products may enhance the anti-oxidative defense of the bacterium. Amongst others, the results show an up-regulated transcription of genes for biosynthesis of cysteine and vitamin B-12, transport of methionine and vitamin B-12, and DNA synthesis and repair. Simultaneously, transcription of genes for degradation of an anti-oxidant compound is down-regulated in a HbpSc-SenSc-SenRc-dependent manner. It appears that HbpSc-SenSc-SenRc controls the non-enzymatic response of Streptomyces coelicolor A3(2) to counteract the hazardous effects of oxidative stress. Binding of the response regulator SenRc to regulatory regions of some of the studied genes indicates that the regulation is direct. The results additionally suggest that HbpSc-SenSc-SenRc may act in concert with other regulatory modules such as a transcriptional regulator, a two-component system and the Streptomyces B-12 riboswitch. The transcriptomics data, together with our previous in vitro results, enable a profound characterization of the HbpS-SenS-SenR system from streptomycetes. Since homologues to HbpS-SenS-SenR are widespread in different actinobacteria with ecological and medical relevance, the data presented here will serve as a basis to elucidate the biological role of these homologues

From waste to health-supporting molecules: biosynthesis of natural products from lignin-, plastic- and seaweed-based monomers using metabolically engineered Streptomyces lividans

Background Transforming waste and nonfood materials into bulk biofuels and chemicals represents a major stride in creating a sustainable bioindustry to optimize the use of resources while reducing environmental footprint. However, despite these advancements, the production of high-value natural products often continues to depend on the use of frst-generation substrates, underscoring the intricate processes and specifc requirements of their bio‑ syntheses. This is also true for Streptomyces lividans, a renowned host organism celebrated for its capacity to produce a wide array of natural products, which is attributed to its genetic versatility and potent secondary metabolic activ‑ ity. Given this context, it becomes imperative to assess and optimize this microorganism for the synthesis of natural products specifcally from waste and nonfood substrates. Results We metabolically engineered S. lividans to heterologously produce the ribosomally synthesized and post‑ translationally modifed peptide bottromycin, as well as the polyketide pamamycin. The modifed strains success‑ fully produced these compounds using waste and nonfood model substrates such as protocatechuate (derived from lignin), 4-hydroxybenzoate (sourced from plastic waste), and mannitol (from seaweed). Comprehensive tran‑ scriptomic and metabolomic analyses ofered insights into how these substrates infuenced the cellular metabolism of S. lividans. In terms of production efciency, S. lividans showed remarkable tolerance, especially in a fed-batch process using a mineral medium containing the toxic aromatic 4-hydroxybenzoate, which led to enhanced and highly selective bottromycin production. Additionally, the strain generated a unique spectrum of pamamycins when cul‑ tured in mannitol-rich seaweed extract with no additional nutrients. Conclusion Our study showcases the successful production of high-value natural products based on the use of var‑ ied waste and nonfood raw materials, circumventing the reliance on costly, food-competing resources. S. lividans exhibited remarkable adaptability and resilience when grown on these diverse substrates. When cultured on aromatic compounds, it displayed a distinct array of intracellular CoA esters, presenting promising avenues for polyketide pro‑ duction. Future research could be focused on enhancing S. lividans substrate utilization pathways to process the intri‑ cate mixtures commonly found in waste and nonfood sources more efciently

Streptomyces spp. From the Marine Sponge Antho dichotoma: Analyses of Secondary Metabolite Biosynthesis Gene Clusters and Some of Their Products

Guerrero-Garzón JF, Zehl M, Schneider O, et al. Streptomyces spp. From the Marine Sponge Antho dichotoma: Analyses of Secondary Metabolite Biosynthesis Gene Clusters and Some of Their Products. Frontiers in Microbiology. 2020;11: 437.Actinomycete bacteria from marine environments represent a potential source for new antibiotics and anti-tumor drugs. Ten strains belonging to the genus Streptomyces isolated from the marine sponge Antho dichotoma collected at the bottom of the Trondheim fjord (Norway) were screened for antibiotic activity. Since only few isolates proved to be bioactive in the conditions tested, we decided to gain an insight into their biosynthetic potential using genome sequencing and analysis. Draft genomes were analyzed for the presence of secondary metabolite biosynthesis gene clusters (BGCs) using antiSMASH software. BGCs specifying both known and potentially novel secondary metabolites were identified, suggesting that these isolates might be sources for new bioactive compounds. The results of this analysis also implied horizontal transfer of several gene clusters between the studied isolates, which was especially evident for the lantibiotic- and thiopeptide-encoding BGCs. The latter implies the significance of particular secondary metabolites for the adaptation of Streptomyces to the spatially enclosed marine environments such as marine sponges. Two bioactive isolates, one showing activity against both yeast and Bacillus subtilis, and one only against yeast were analyzed in details, leading to the identification of cycloheximide, linearmycins, and echinomycins that are presumably responsible for the observed bioactivities

Actinoalloteichus fjordicus sp. nov. isolated from marine sponges: phenotypic, chemotaxonomic and genomic characterisation.

Nouioui I, Rückert C, Willemse J, et al. Actinoalloteichus fjordicus sp. nov. isolated from marine sponges: phenotypic, chemotaxonomic and genomic characterisation. Antonie Van Leeuwenhoek. Journal of Microbiology. 2017;110(12):1705-1717.Two actinobacterial strains, ADI 127-17T and GBA 129-24, isolated from marine sponges Antho dichotoma and Geodia barretti, respectively, collected at the Trondheim fjord in Norway, were the subjects of a polyphasic study. According to their 16S rRNA gene sequences, the new isolates were preliminarily classified as belonging to the genus Actinoalloteichus. Both strains formed a distinct branch, closely related to the type strains of Actinoalloteichus hoggarensis and Actinoalloteichus hymeniacidonis, within the evolutionary radiation of the genus Actinoalloteichus in the 16S rRNA gene-based phylogenetic tree. Isolates ADI 127-17T and GBA 129-24 exhibited morphological, chemotaxonomic and genotypic features distinguishable from their close phylogenetic neighbours. Digital DNA: DNA hybridization and ANI values between strains ADI 127-17T and GBA 129-24 were 97.6 and 99.7%, respectively, whereas the corresponding values between both tested strains and type strains of their closely related phylogenetic neighbours, A. hoggarensis and A. hymeniacidonis, were well below the threshold for delineation of prokaryotic species. Therefore, strains ADI 127-17T (= DSM 46855T) and GBA 129-24 (= DSM 46856) are concluded to represent a novel species of the genus Actinoalloteichus for which the name of Actinoalloteichus fjordicus sp. nov. (type strain ADI 127-17T = DSM 46855T = CECT 9355T) is proposed. The complete genome sequences of the new strains were obtained and compared to that of A. hymeniacidonis DSM 45092T and A. hoggarensis DSM 45943T to unravel unique genome features and biosynthetic potential of the new isolates

Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress.

Hillion M, Bernhardt J, Busche T, et al. Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress. Sci Rep. 2017;7(1): 1195.Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes. Here, we used shotgun proteomics, OxICAT and RNA-seq transcriptomics to analyse protein S-mycothiolation, reversible thiol-oxidations and their impact on gene expression in Mycobacterium smegmatis under hypochlorite stress. In total, 58 S-mycothiolated proteins were identified under NaOCl stress that are involved in energy metabolism, fatty acid and mycolic acid biosynthesis, protein translation, redox regulation and detoxification. Protein S-mycothiolation was accompanied by MSH depletion in the thiol-metabolome. Quantification of the redox state of 1098 Cys residues using OxICAT revealed that 381 Cys residues (33.6%) showed >10% increased oxidations under NaOCl stress, which overlapped with 40 S-mycothiolated Cys-peptides. The absence of MSH resulted in a higher basal oxidation level of 338 Cys residues (41.1%). The RseA and RshA anti-sigma factors and the Zur and NrdR repressors were identified as NaOCl-sensitive proteins and their oxidation resulted in an up-regulation of the SigH, SigE, Zur and NrdR regulons in the RNA-seq transcriptome. In conclusion, we show here that NaOCl stress causes widespread thiol-oxidation including protein S-mycothiolation resulting in induction of antioxidant defense mechanisms in M. smegmatis. Our results further reveal that MSH is important to maintain the reduced state of protein thiols

Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma

Background: Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma. Objective: The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance. Methods: We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration. Results: Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS. Conclusion: The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma. Keywords: asthma phenotypes; biological therapy; corticosteroids resistance; leukocyte redistribution; severe asthma; treatment asthm

An artificial intelligence algorithm is highly accurate for detecting endoscopic features of eosinophilic esophagitis

The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level

Complete Genome Sequence of Streptomyces lavendulae subsp. lavendulae CCM 3239 (Formerly “Streptomyces aureofaciens CCM 3239”), a Producer of the Angucycline-Type Antibiotic Auricin

Busche T, Novakova R, Al'Dilaimi A, et al. Complete Genome Sequence of Streptomyces lavendulae subsp. lavendulae CCM 3239 (Formerly “Streptomyces aureofaciens CCM 3239”), a Producer of the Angucycline-Type Antibiotic Auricin. Genome Announcements. 2018;6(9): e00103-18.Streptomyces lavendulae subsp. lavendulae CCM 3239 produces the angucycline antibiotic auricin and was thought to be the type strain of Streptomyces aureofaciens. We report the complete genome sequence of this strain, which consists of a linear chromosome and the linear plasmid pSA3239, and demonstrate it to be S. lavendulae subsp. lavendulae

The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response

Background: Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. Methods: 110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR. Results: The median age of the patients was 16 years (range 3–60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05). Conclusions: Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects