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Molecules (Basel, Switzerland) Nov 2022Large scale cultivation and chemical investigation of an extract obtained from sp. resulted in the identification of six previously undescribed spirotetronates...
Large scale cultivation and chemical investigation of an extract obtained from sp. resulted in the identification of six previously undescribed spirotetronates (pyrrolosporin B and decatromicins C-G; -), along with six known congeners, namely decatromicins A-B (-), BE-45722B-D (-), and pyrrolosporin A (). The chemical structures of compounds - were characterized via comparison with previously reported data and analysis of 1D/2D NMR and MS data. The structures of all new compounds were highly related to the spirotetronate type compounds, decatromicin and pyrrolosporin, with variations in the substituents on the pyrrole and aglycone moieties. All compounds were evaluated for antibacterial activity against the Gram-negative bacteria, and Gram-positive bacteria, and were investigated for their cytotoxicity against the human cancer cell line A549. Of these, decatromicin B (), BE-45722B (), and pyrrolosporin B () exhibited potent antibacterial activities against both Gram-positive (MIC between 1-3 μM) and Gram-negative bacteria (MIC values ranging from 12-36 μM) with weak or no cytotoxic activity against A549 cells.
Topics: Humans; Polyketides; Actinomadura; Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests
PubMed: 36500287
DOI: 10.3390/molecules27238196 -
Applied and Environmental Microbiology May 2022Nonheme iron- and α-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C()-H bonds,...
Nonheme iron- and α-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C()-H bonds, exhibit tremendous potential in the challenging asymmetric halogenation. AdeV from Actinomadura sp. ATCC 39365 is the first identified carrier protein-free NHFeHal that catalyzes the chlorination of nucleotide 2'-deoxyadenosine-5'-monophosphate (2'-dAMP) to afford 2'-chloro-2'-deoxyadenosine-5'-monophosphate. Here, we determined the complex crystal structures of AdeV/Fe/Cl and AdeV/Fe/Cl/αKG at resolutions of 1.76 and 1.74 Å, respectively. AdeV possesses a typical β-sandwich topology with H194, H252, αKG, chloride, and one water molecule coordinating Fe in the active site. Molecular docking, mutagenesis, and biochemical analyses reveal that the hydrophobic interactions and hydrogen bond network between the substrate-binding pocket and the adenine, deoxyribose, and phosphate moieties of 2'-dAMP are essential for substrate recognition. Residues H111, R177, and H192 might play important roles in the second-sphere interactions that control reaction partitioning. This study provides valuable insights into the catalytic selectivity of AdeV and will facilitate the rational engineering of AdeV and other NHFeHals for synthesis of halogenated nucleotides. Halogenated nucleotides are a group of important antibiotics and are clinically used as antiviral and anticancer drugs. AdeV is the first carrier protein-independent nonheme iron- and α-ketoglutarate (αKG)-dependent halogenase (NHFeHal) that can selectively halogenate nucleotides and exhibits restricted substrate specificity toward several 2'-dAMP analogues. Here, we determined the complex crystal structures of AdeV/Fe/Cl and AdeV/Fe/Cl/αKG. Molecular docking, mutagenesis, and biochemical analyses provide important insights into the catalytic selectivity of AdeV. This study will facilitate the rational engineering of AdeV and other carrier protein-independent NHFeHals for synthesis of halogenated nucleotides.
Topics: Carrier Proteins; Ferrous Compounds; Halogenation; Halogens; Iron; Ketoglutaric Acids; Molecular Docking Simulation; Nucleotides
PubMed: 35435717
DOI: 10.1128/aem.02497-21 -
Frontiers in Microbiology 2024While spent mushroom substrate (SMS) has shown promise in increasing soil organic carbon (SOC) and improving soil quality, research on the interplay between SOC...
While spent mushroom substrate (SMS) has shown promise in increasing soil organic carbon (SOC) and improving soil quality, research on the interplay between SOC components and microbial community following the application of diverse SMS types remains scant. A laboratory soil incubation experiment was conducted with application of two types of SMSs from cultivation of (PE) and (AB), each at three application rates (3, 5.5, and 8%). Advanced techniques, including solid-state C nuclear magnetic resonance (NMR) and high-throughput sequencing, were employed to investigate on SOC fractions and chemical structure, microbial community composition and functionality. Compared to SMS-AB, SMS-PE application increased the relative abundances of carbohydrate carbon and O-alkyl C in SOC. In addition, SMS-PE application increased the relative abundance of the bacterial phylum Proteobacteria and those of the fungal phyla Basidiomycota and Ascomycota. The relative abundances of cellulose-degrading bacterial (e.g., and ) and fungal genera (e.g., , , and ) were increased as well. The application of SMS-AB increased the aromaticity index of SOC, the relative abundance of aromatic C, and the contents of humic acid and heavy fraction organic carbon. In addition, SMS-AB application significantly increased the relative abundances of the bacterial phyla Firmicutes and Actinobacteria. Notably, the genera , , and , which were positively correlated with humic acid, experienced an increase in relative abundance. Functional prediction revealed that SMS-PE application elevated carbohydrate metabolism and reduced the prevalence of fungal pathogens, particularly . The application of high-rate SMS-AB (8%) enhanced bacterial amino acid metabolism and the relative abundances of plant pathogenic fungi. Our research provides strategies for utilizing SMS to enrich soil organic carbon and fortify soil health, facilitating the achievement of sustainable soil management.
PubMed: 38827156
DOI: 10.3389/fmicb.2024.1351921 -
Saudi Journal of Biological Sciences Jun 2022Fungi colonizing fruits in the field and post-harvest constitute a major threat to the global food sector. This study focuses on the biocontrol of (aflatoxin-producing...
Fungi colonizing fruits in the field and post-harvest constitute a major threat to the global food sector. This study focuses on the biocontrol of (aflatoxin-producing mold considered carcinogenic by IARC) and f. sp. albedinis (FOA) (phytopathogenic agent, causal of El Bayoud in the Algerian and Moroccan Sahara). These molds have a significant economic impact and pose a serious human health problem. The aim of this work is to study the antifungal activity of two rare actinomycetes strains; sp. COL22 and sp. COL08 strains against toxinogenic and . f. sp. albedinis. The strains are isolated from rhizosphere on different media: ISP2, GLM, TSA, Starch-casein-agar and WYE and with different treatments of the samples (physical, chemical treatment and enrichment). The antifungal tests against the pathogenic microorganisms were performed on ISP2, GLM and TSA medium by means of the agar cylinders method. The kinetics of antibiotic production were performed on ISP medium over 16 days. The characterization of the antimicrobial compounds by LC-ESI/MS-MS showed that the bacterial extracts contain Antibiotic SF 2738C, Tetrodecamycin and Aplysillamide B. The phenotypic and molecular studies showed that sp. COL22 is closely related to the strain type and that sp. COL08 is closely related to the strain type. The two strains are rare and showed an interesting activity against toxinogenic and f. sp. albedinis.
PubMed: 35574281
DOI: 10.1016/j.sjbs.2022.103288 -
Scientific Reports May 2022Mucin-degrading microbes are known to harbor glycosyl hydrolases (GHs) which cleave specific glycan linkages. Although several microbial species have been identified as...
Mucin-degrading microbes are known to harbor glycosyl hydrolases (GHs) which cleave specific glycan linkages. Although several microbial species have been identified as mucin degraders, there are likely many other members of the healthy gut community with the capacity to degrade mucins. The aim of the present study was to systematically examine the CAZyme mucin-degrading profiles of the human gut microbiota. Within the Verrucomicrobia phylum, all Akkermansia glycaniphila and muciniphila genomes harbored multiple gene copies of mucin-degrading GHs. The only representative of the Lentisphaerae phylum, Victivallales, harbored a GH profile that closely mirrored Akkermansia. In the Actinobacteria phylum, we found several Actinomadura, Actinomyces, Bifidobacterium, Streptacidiphilus and Streptomyces species with mucin-degrading GHs. Within the Bacteroidetes phylum, Alistipes, Alloprevotella, Bacteroides, Fermenitomonas Parabacteroides, Prevotella and Phocaeicola species had mucin degrading GHs. Firmicutes contained Abiotrophia, Blautia, Enterococcus, Paenibacillus, Ruminococcus, Streptococcus, and Viridibacillus species with mucin-degrading GHs. Interestingly, far fewer mucin-degrading GHs were observed in the Proteobacteria phylum and were found in Klebsiella, Mixta, Serratia and Enterobacter species. We confirmed the mucin-degrading capability of 23 representative gut microbes using a chemically defined media lacking glucose supplemented with porcine intestinal mucus. These data greatly expand our knowledge of microbial-mediated mucin degradation within the human gut microbiota.
Topics: Animals; Clostridiales; Gastrointestinal Microbiome; Humans; Mucins; Polysaccharides; Swine; Verrucomicrobia
PubMed: 35589783
DOI: 10.1038/s41598-022-11819-z -
Indian Dermatology Online Journal 2021Mycetoma is a chronic, granulomatous disease caused by fungi (eumycetoma) or aerobic filamentous actinomycetes (actinomycetoma). is one of the most frequent...
CONTEXT
Mycetoma is a chronic, granulomatous disease caused by fungi (eumycetoma) or aerobic filamentous actinomycetes (actinomycetoma). is one of the most frequent actinomycetes.
AIM
The study aims to provide an update on clinical, diagnostic, therapeutic, and outcome data for patients with actinomycetoma in a single center in Mexico.
SETTINGS AND DESIGN
This was a retrospective study of 47 cases diagnosed with actinomycetoma.
SUBJECTS AND METHODS
The cases were selected from a total of 536 mycetoma obtained during 35 years (from 1985 to 2019). Clinical data were retrieved from the clinical records of our department. Microbiological data were obtained from our Mycology laboratory.
STATISTICAL ANALYSIS
Frequencies and percentages were used for categorical variables. Normality was determined with the Kolmogorov-Smirnov test. We used means and medians to describe the variables.
RESULTS
Forty-seven patients with actinomycetoma were included; female:male ratio 1.9:1; median age 38 years. The foot was the most affected region in 76.5% of cases. The bone invasion was observed in 89%. The time between symptoms onset and diagnosis was 5.5 years. Grain detection by direct examination was positive in 95% of cases. The most commonly used, as well as the most effective treatment scheme was streptomycin + sulfamethoxazole-trimethoprim with dapsone. Sixty-three percent (30 patients) achieved clinical and mycological cure, and 10.6% (5 patients) had treatment failure.
CONCLUSIONS
We highlight the importance of designing therapeutic strategies to standardize treatments and gain more experience to improve the care of these patients.
PubMed: 33959526
DOI: 10.4103/idoj.IDOJ_474_20 -
PLoS Neglected Tropical Diseases Jul 2019Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative...
Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative agents organise themselves in macroscopic structures called grains. These grains are surrounded by a massive inflammatory reaction. The processes leading to this host tissue reaction and the immunophenotypic characteristics of the mycetoma granuloma are not known. Due to the massive immune reaction and the tissue remodeling involved, we hypothesised that the expression levels of interleukin-17 (IL-17) and matrix metalloprotease-9 (MMP-9) in the mycetoma granuloma formation were correlated to the severity of the disease and that this correlation was independent of the causative agent responsible for the granuloma reaction. To determine the expression of IL-17 and MMP-9 in mycetoma lesions, the present study was conducted at the Mycetoma Research Centre, Sudan. Surgical biopsies from 100 patients with confirmed mycetoma were obtained, and IL-17 and MMP-9 expression in the mycetoma granuloma were evaluated immunohistochemically. IL-17 was mainly expressed in Zones I and II, and far less in Zone III. MMP-9 was detected mainly in Zones II and III, and the least expression was in Zone I. MMP-9 was more highly expressed in Actinomadura pelletierii and Streptomyces somaliensis biopsies compared to Madurella mycetomatis biopsies. MMP-9 levels were directly proportional to the levels of IL-17 (p = 0.001). The only significant association between MMP9 and the patients' characteristics was the disease duration (p<0.001). There was an insignificant correlation between the IL-17 levels and the patients' demographic characteristics.
Topics: Actinobacteria; Actinomadura; Adolescent; Adult; Biopsy; Child; Collagen; Female; Gene Expression; Granuloma; Humans; Immunohistochemistry; Interleukin-17; Madurella; Male; Matrix Metalloproteinase 9; Middle Aged; Mycetoma; Qualitative Research; Severity of Illness Index; Streptomyces; Sudan; Young Adult
PubMed: 31295246
DOI: 10.1371/journal.pntd.0007351 -
The Pan African Medical Journal 2019Mycetoma is a chronic inflammatory process during which exogenous fungal or actinomycosic agents produce grains. The infection involves the skin, the subcutaneous...
Mycetoma is a chronic inflammatory process during which exogenous fungal or actinomycosic agents produce grains. The infection involves the skin, the subcutaneous tissues, the muscles and the bones. We report the case of a 39-year old woman, a teacher, living in Brazzaville, who had regularly resided in the village. She presented with a painless suppurative mass in the left thigh that had been treated with bandages over the past 4 years. The patient didn't have fever. Her general condition was good. Physical examination showed poly-lobed, firm tumor mass in the posterior surface of the left thigh, measuring 11cm in diameter on the major axis, with ulcerations discharging purulent serosity. There was no satellite adenopathy. The remainder of the physical examination was normal. Bacteriological analysis showed sterile serosity. Skin biopsy revealed alteration of the connective tissue and the presence of small foci of grains, typical of Actinomadura pelletieri. CRP level was 48mg/L; blood count, blood glucose, blood lipids and LDH were normal. Standard radiography of the affected thigh was normal. The diagnosis of actinomycosic mycetoma was retained. Patient's outcome, after a 12-month treatment with cotrimoxazole, was marked by the epidermization of the ulcers and the persistence of the tumor mass, justifying secondary surgical resection.
PubMed: 32153703
DOI: 10.11604/pamj.2019.34.163.20300 -
PLoS Neglected Tropical Diseases Aug 2019Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper...
Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper treatment. In endemic areas, various diagnostic tests and techniques are in use to achieve that, and that includes grain culture, surgical biopsy histopathological examination, fine needle aspiration cytological (FNAC) examination and in certain centres molecular diagnosis such as PCR. In this retrospective study, the sensitivity, specificity and diagnostic accuracy of grain culture, surgical biopsy histopathological examination and FNAC to identify the mycetoma causative organisms were determined. The histopathological examination appeared to have better sensitivity and specificity. The histological examination results were correct in 714 (97.5%) out of 750 patients infected with Madurella mycetomatis, in 133 (93.6%) out of 142 patients infected with Streptomyces somaliensis, in 53 (74.6%) out of 71 patients infected with Actinomadura madurae and in 12 (75%) out of 16 patients infected with Actinomadura pelletierii. FNAC results were correct in 604 (80.5%) out of 750 patients with Madurella mycetomatis eumycetoma, in 50 (37.5%) out of 133 Streptomyces somaliensis patients, 43 (60.5%) out of 71 Actinomadura madurae patients and 11 (68.7%) out of 16 Actinomadura pelletierii. The mean time required to obtain the FNAC result was one day, and for the histopathological examinations results it was 3.5 days, and for grain it was a mean of 16 days. In conclusion, histopathological examination and FNAC are more practical techniques for rapid species identification than grain culture in many endemic regions.
Topics: Actinobacteria; Actinomadura; Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Madurella; Male; Middle Aged; Mycetoma; Pathology, Molecular; Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Streptomyces; Young Adult
PubMed: 31465459
DOI: 10.1371/journal.pntd.0007056 -
Journal of Xenobiotics Aug 2023The decomposition of biodegradable composite carbon sources generates a large amount of biodegradable microplastics, which may not only furnish microbial...
The decomposition of biodegradable composite carbon sources generates a large amount of biodegradable microplastics, which may not only furnish microbial denitrification, but might also pose potential environmental risks. In the present study, the effects of different dosages of a biodegradable composite carbon source on the microbial communities, the nitrogen metabolic pathways and the antibiotic resistome were explored through Illumina MiSeq sequencing analysis and metagenomic analysis. The results of partial least-square discriminant analysis (PLS-DA) and analysis of similarity (ANOSIM) demonstrated that the response of the bacterial community to a biodegradable composite carbon source was more obvious than the fungal community. The application of biodegradable microplastics diminished the complexity of the microbial communities to some extent and obviously stimulated denitrification. Antibiotics resistance gene (ARG) dispersal was not evidently accelerated after the addition of biodegradable composite carbon source. , , , , from and , , and from were the major ARG hosts. Overall, the addition of a biodegradable composite carbon source shaped microbial communities and their antibiotic resistance profiles in this study.
PubMed: 37606424
DOI: 10.3390/jox13030027