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Organic Letters Feb 2020Forazoline A is a structurally complex PKS-NRPS hybrid produced by marine-derived sp. During the course of studies highlighting the application of IFS analysis as a...
Forazoline A is a structurally complex PKS-NRPS hybrid produced by marine-derived sp. During the course of studies highlighting the application of IFS analysis as a powerful tool for natural products analysis, we were alerted to an earlier misinterpretation with respect to forazoline A structure elucidation. In particular, IFS reveals that forazoline A contains a thioketone moiety rarely seen in secondary metabolites and, thus, constitutes an even more intriguing structure than originally thought.
Topics: Actinomycetales; Biological Products; Isotopes; Mass Spectrometry; Molecular Conformation; Polyketides
PubMed: 32017574
DOI: 10.1021/acs.orglett.9b04535 -
BioMed Research International 2020Meyer, a valuable medicinal plant, is severely threatened by rusty root, a condition that greatly affects its yield and quality. Studies investigating the relationship...
Meyer, a valuable medicinal plant, is severely threatened by rusty root, a condition that greatly affects its yield and quality. Studies investigating the relationship between soil microbial community composition and rusty roots are vital for the production of high-quality ginseng. Here, high-throughput sequencing was employed to systematically characterize changes in the soil microbial community associated with rusty roots. Fungal diversity was lower in the soils of rusty root-affected than in those of healthy plants. Importantly, principal coordinate analysis separated the fungal communities in the rhizosphere soils of rusty root-affected ginseng from those of healthy plants. The dominant bacterial and fungal genera differed significantly between rhizosphere soils of healthy and rusty root-affected , and linear discriminant analysis effect size (LEfSe) further indicated a strong imbalance in the soil microbial community of diseased plants. Significantly enriched bacterial genera (including , , , , and ) were mainly detected in the soil of rusty root-affected , whereas significantly enriched fungal genera (including , , , , and ) were primarily detected in the soil of healthy plants. Importantly, five fungal genera (, , , , and ) were significantly enriched in the soil of rusty root-affected plants compared with that of healthy plants, suggesting that an increase in the relative abundance of these pathogenic fungi (, , and ) may be associated with ginseng rusty roots. Additionally, this study is the first to report that an increase in the relative abundances of and in the rhizosphere of may be associated with the onset of rusty root symptoms in this plant. Our findings provide potentially useful information for developing biological control strategies against rusty root, as well as scope for future screening of fungal pathogens in rusty roots of .
Topics: Bacteria; Fungi; High-Throughput Nucleotide Sequencing; Microbiota; Panax notoginseng; Plant Diseases; Plant Roots; Rhizosphere; Soil Microbiology
PubMed: 32016120
DOI: 10.1155/2020/8018525 -
Emerging Infectious Diseases Feb 2020Mycetoma is a chronic infection that is slow to develop and heal. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). We describe a case of...
Mycetoma is a chronic infection that is slow to develop and heal. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). We describe a case of actinomycetoma caused by Actinomadura mexicana in the Caribbean region.
Topics: Actinomadura; Adult; Caribbean Region; Diagnosis, Differential; Female; Foot Dermatoses; Humans; Mycetoma
PubMed: 31961313
DOI: 10.3201/eid2602.191005 -
Frontiers in Microbiology 2019The amendment of crop residues produced under elevated CO (eCO) may alter soil microbial community structure and their functions on residue decomposition and carbon (C)...
The amendment of crop residues produced under elevated CO (eCO) may alter soil microbial community structure and their functions on residue decomposition and carbon (C) cycling in soil. The key to understanding this process is to elucidate the structure of prokaryotic communities that metabolize crop residues derived from eCO. A soil incubation experiment was conducted to explore the response of soil microbial community to the amendment of C-labeled soybean residues produced under ambient CO (aCO) and eCO The residues were applied to a Mollisol, followed by C-DNA stable isotope probing (SIP) and Illumina sequencing on soil prokaryotic community over time. The structure of residue-metabolizing community differed in response to the amendment of eCO- and aCO-derived residues after 28 days of incubation. In particular, genera , , , and were the dominant members of the residue-metabolizing bacteria, which contributed to this difference. The relative abundances of genera , and were 118-144%, 71-113%, and 2-4-fold higher in the Mollisol amended with aCO-derived than eCO-derived residue. In contrast, the relative abundance of was 87-90% greater in the eCO-residue treatment. However, during the incubation period, there was no difference between the two residue treatments in the community structure as a whole without SIP. These results implied that a pioneering prokaryotic community metabolized the residue initially prior to the entire community. Those bacteria genera being inhibited with the amendment of the eCO-derived residue, compared to aCO-derived residue, were likely preferential to metabolize recalcitrant C, which might be associated with changes of chemical composition of the residue under eCO.
PubMed: 31681180
DOI: 10.3389/fmicb.2019.02184 -
Journal of Virology Jan 2020To counteract the serious health threat posed by known and novel viral pathogens, drugs that target a variety of viruses through a common mechanism have attracted recent...
To counteract the serious health threat posed by known and novel viral pathogens, drugs that target a variety of viruses through a common mechanism have attracted recent attention due to their potential in treating (re)emerging infections, for which direct-acting antivirals are not available. We found that labyrinthopeptins A1 and A2, the prototype congeners of carbacyclic lanthipeptides, inhibit the proliferation of diverse enveloped viruses, including dengue virus, Zika virus, West Nile virus, hepatitis C virus, chikungunya virus, Kaposi's sarcoma-associated herpesvirus, cytomegalovirus, and herpes simplex virus, in the low micromolar to nanomolar range. Mechanistic studies on viral particles revealed that labyrinthopeptins induce a virolytic effect through binding to the viral membrane lipid phosphatidylethanolamine (PE). These effects are enhanced by a combined equimolar application of both labyrinthopeptins, and a clear synergism was observed across a concentration range corresponding to 10% to 90% inhibitory concentrations of the compounds. Time-resolved experiments with large unilamellar vesicles (LUVs) reveal that membrane lipid raft compositions (phosphatidylcholine [PC]/PE/cholesterol/sphingomyelin at 17:10:33:40) are particularly sensitive to labyrinthopeptins in comparison to PC/PE (90:10) LUVs, even though the overall PE amount remains constant. Labyrinthopeptins exhibited low cytotoxicity and had favorable pharmacokinetic properties in mice (half-life [] = 10.0 h), which designates them promising antiviral compounds acting by an unusual viral lipid targeting mechanism. For many viral infections, current treatment options are insufficient. Because the development of each antiviral drug is time-consuming and expensive, the prospect of finding broad-spectrum antivirals that can fight multiple, diverse viruses-well-known viruses as well as (re)emerging species-has gained attention, especially for the treatment of viral coinfections. While most known broad-spectrum agents address processes in the host cell, we found that targeting lipids of the free virus outside the host cell with the natural products labyrinthopeptin A1 and A2 is a viable strategy to inhibit the proliferation of a broad range of viruses from different families, including chikungunya virus, dengue virus, Zika virus, Kaposi's sarcoma-associated herpesvirus, and cytomegalovirus. Labyrinthopeptins bind to viral phosphatidylethanolamine and induce virolysis without exerting cytotoxicity on host cells. This represents a novel and unusual mechanism to tackle medically relevant viral infections.
Topics: Aedes; Animals; Bacteriocins; Cell Line; Membrane Microdomains; Phosphatidylethanolamines; Virus Diseases; Viruses
PubMed: 31666384
DOI: 10.1128/JVI.01471-19 -
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 -
Organic Letters Aug 2019Two new siderophores, madurastatin D1 and D2, together with (-)-madurastatin C1, the enantiomer of a known compound, were isolated from marine-derived sp. The presence...
Two new siderophores, madurastatin D1 and D2, together with (-)-madurastatin C1, the enantiomer of a known compound, were isolated from marine-derived sp. The presence of an unusual 4-imidazolidinone ring in madurastatins D1 and D2 inspired us to sequence the sp. genome and to identify the biosynthetic gene cluster, knowledge of which enables us to now propose a biosynthetic pathway. Madurastatin D1 and D2 are moderately active in antimicrobial assays with .
Topics: Actinomycetales; Anti-Bacterial Agents; Genome, Bacterial; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Micrococcus luteus; Molecular Structure; Multigene Family; Oligopeptides; Oxazoles; Piperidones; Siderophores; Stereoisomerism
PubMed: 31380646
DOI: 10.1021/acs.orglett.9b02159 -
RSC Advances Jul 2019Actinomycetes are outstanding and fascinating sources of potent bioactive compounds, particularly antibiotics. In recent years, rare actinomycetes have had an... (Review)
Review
Actinomycetes are outstanding and fascinating sources of potent bioactive compounds, particularly antibiotics. In recent years, rare actinomycetes have had an increasingly important position in the discovery of antibacterial compounds, especially , and . Focusing on the period from 2008 to 2018, we herein summarize the structures and bioactivities of secondary metabolites from rare actinomycetes, involving 21 genera.
PubMed: 35518871
DOI: 10.1039/c9ra03579f -
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 Journal of General and Applied... Sep 2019Spirotetronate compounds are polyketide secondary metabolites with diverse biological functions, such as antibacterial, antitumor and antiviral activities. Three pure...
Spirotetronate compounds are polyketide secondary metabolites with diverse biological functions, such as antibacterial, antitumor and antiviral activities. Three pure spirotetronate compounds (2EPS-A, -B, -C) isolated from Actinomadura strain 2EPS showed inhibitory activity against dengue virus serotype 2 (DENV-2). 2EPS-A, -B and -C demonstrated the LC values of 11.6, 27.5 and 12.0 μg/ml, respectively, in a test of cytotoxicity to Vero cells. The least cytotoxic, 2EPS-B, was further analyzed for its impact on viral propagation in a cell-based replication assay. At a concentration of 6.25 μg/ml, it could reduce the DENV-2 infection in Vero cells by about 94% when cells infected with DENV-2 were exposed to 2EPS-B, whereas direct treatment of DENV-2 with 2EPS-B at the same concentration prior to subsequent infection to Vero cell yielded no inhibition. 2EPS-A, -B an -C showed strong DENV-2 NS2B-NS3 protease inhibition in an in vitro assay, with IC values of 1.94 ± 0.18, 1.47 ± 0.15 and 2.51 ± 0.21 μg/ml, respectively. Therefore, the spirotetronate compounds appear to prevent viral replication and viral assembly by inhibition of the viral protease.
Topics: Actinobacteria; Animals; Antiviral Agents; Chlorocebus aethiops; Dengue Virus; Inhibitory Concentration 50; Polyketides; Protease Inhibitors; Serogroup; Vero Cells; Virus Replication
PubMed: 30814437
DOI: 10.2323/jgam.2018.10.001