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1.
Environ Res ; 252(Pt 4): 119151, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38754608

RESUMEN

The aim of this study was to assess effects of MnO2 addition (CK-0%, T1-2% and T2-5%) on humification and bacterial community during municipal sludge (MS) composting. The results suggested that MnO2 addition inhibited the growth of Nitrospira but stimulated Nonomuraea, Actinomadura, Streptomyces and Thermopolyspora, facilitating the lignocellulose degradation and humification with the increase in organic matter degradation by 13.8%-19.2% and humic acid content by 10.9%-20.6%. Compared to CK, the abundances of exoglucanase (EC:3.2.1.91), endo-1,4-beta-xylanase (EC:3.2.1.136) and endomannanase (EC:3.2.1.78) increased by 88-99, 52-66 and 4-15 folds, respectively. However, 5%-MnO2 induced the enrichment of Mizugakiibacter that harms the environment of agricultural production. The addition of 2%-MnO2 was recommended for MS composting. Furthermore, metabolic function analysis indicated that MnO2 addition altered amino acid and carbohydrate metabolism, especially enhancing propanoate metabolism and butanoate metabolism but inhibiting citrate cycle. Structural equation modeling revealed that Nonomuraea and Actinomadura were the main drivers for lignocellulose degradation. This study provided theoretical guidance in regulating humification via MnO2 for MS composting.


Asunto(s)
Compostaje , Eliminación de Residuos Líquidos , Compostaje/métodos , Eliminación de Residuos Líquidos/métodos , Microbiología del Suelo , Biodegradación Ambiental , Suelo , Actinobacteria , Actinomadura , Streptomyces , Sustancias Húmicas
2.
J Nat Prod ; 87(5): 1471-1478, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38747559

RESUMEN

A chemical investigation of Australian soil-derived bacteria Actinomadura sp. S4S-00069B08 yielded eight new benzenoid ansamycins, goondansamycins A-H. Goondansamycins feature rare 1,4-benzoxazin-3-one or o-diamino-p-benzoquinone moieties and can exist as both aglycones or 9-O-α-glycosides of either d-rhodinose or d-amicetose. Structures were solved on the basis of detailed spectroscopy, including X-ray analysis.


Asunto(s)
Actinomadura , Microbiología del Suelo , Australia , Estructura Molecular , Benzoquinonas/química , Benzoquinonas/farmacología , Cristalografía por Rayos X
3.
Antimicrob Agents Chemother ; 68(5): e0161223, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38602413

RESUMEN

Mycetoma is a devastating neglected tropical infection of the subcutaneous tissues. It is caused by fungal and bacterial pathogens recognized as eumycetoma and actinomycetoma, respectively. Mycetoma treatment involves diagnosing the causative microorganism as a prerequisite to prescribing a proper medication. Current therapy of fungal eumycetoma causative agents, such as Madurella mycetomatis, consists of long-term antifungal medication with itraconazole followed by surgery, yet with usually unsatisfactory clinical outcomes. Actinomycetoma, on the contrary, usually responds to treatment with co-trimoxazole and amikacin. Therefore, there is a pressing need to discover novel broad-spectrum antimicrobial agents to circumvent the time-consuming and costly diagnosis. Using the resazurin assay, a series of 23 naphthylisoquinoline (NIQ) alkaloids and related naphthoquinones were subjected to in vitro screening against two fungal strains of M. mycetomatis and three bacterial strains of Actinomadura madurae and A. syzygii. Seven NIQs, mostly dimers, showed promising in vitro activities against at least one strain of the mycetoma-causative pathogens, while the naphthoquinones did not show any activity. A synthetic NIQ dimer, 8,8'''-O,O-dimethylmichellamine A (18), inhibited all tested fungal and bacterial strains (IC50 = 2.81-12.07 µg/mL). One of the dimeric NIQs, michellamine B (14), inhibited a strain of M. mycetomatis and significantly enhanced the survival rate of Galleria mellonella larvae infected with M. mycetomatis at concentrations of 1 and 4 µg/mL, without being toxic to the uninfected larvae. As a result, broad-spectrum dimeric NIQs like 14 and 18 with antimicrobial activity are considered hit compounds that could be worth further optimization to develop novel lead antimycetomal agents.


Asunto(s)
Alcaloides , Antifúngicos , Madurella , Pruebas de Sensibilidad Microbiana , Micetoma , Micetoma/tratamiento farmacológico , Micetoma/microbiología , Antifúngicos/farmacología , Animales , Alcaloides/farmacología , Alcaloides/química , Madurella/efectos de los fármacos , Isoquinolinas/farmacología , Actinomadura/efectos de los fármacos , Naftoquinonas/farmacología , Larva/microbiología , Larva/efectos de los fármacos , Mariposas Nocturnas/microbiología
4.
Fitoterapia ; 173: 105806, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38181893

RESUMEN

Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.


Asunto(s)
Actinomadura , Antineoplásicos , Humanos , Estructura Molecular , Antineoplásicos/farmacología , Línea Celular Tumoral , Antraquinonas
5.
Nat Prod Rep ; 41(3): 370-401, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38099919

RESUMEN

Covering: up to the end of 2022In recent years rare Actinobacteria have become increasingly recognised as a rich source of novel bioactive metabolites. Actinomadura are Gram-positive bacteria that occupy a wide range of ecological niches. This review highlights about 230 secondary metabolites produced by Actinomadura spp., reported until the end of 2022, including their bioactivities and selected biosynthetic pathways. Notably, the bioactive compounds produced by Actinomadura spp. demonstrate a wide range of activities, including antimicrobial, antitumor and anticoccidial effects, highlighting their potential in various fields.


Asunto(s)
Actinobacteria , Antiinfecciosos , Actinomadura , Actinobacteria/metabolismo , Antiinfecciosos/química , Bacterias , Biología
6.
Artículo en Inglés | MEDLINE | ID: mdl-36748505

RESUMEN

Two mycelium-forming actinobacterial strains, designated OS3-83 T and OS3-89, were isolated from rhizosphere soil of a cactus (Opuntia ficus-indica) sampled on Mara Island, Jeju, Republic of Korea. Both of the isolates were found to grow at 20-37 °C, pH 6.0-10.0 and with 0-2 % (w/v) NaCl. Their taxonomic positions were investigated by a polyphasic approach. Strains OS3-83T and OS3-89 were most closely related to the type strain of Actinomadura litoris (99.5 % and 98.9 % 16S rRNA gene sequence similarity, respectively). Both of the isolates shared 99.2 % sequence similarity to each other. Morphological and chemotaxonomic characteristics supported the affiliation of the two isolates to the genus Actinomadura. 16S rRNA gene phylogeny exhibited that strain OS3-83T formed a tight cluster with A. litoris, while strain OS3-89 occupied a position located remotely from A. litoris. Nevertheless, phylogenomic analysis based on 92 core gene sequences showed that both of the isolates formed a tight clade with A. litoris. The values of average nucleotide identity and digital DNA-DNA hybridization between strain OS3-83T and the closest relative, A. litoris, were 92.2 and 46.2 %, respectively, whereas strain OS3-89 shared an average nucleotide identity value of 97.5 % and a digital DNA-DNA hybridization value of 76.9 % with A. litoris. These results strongly suggested that strain OS3-83T (=KACC 19752T=NBRC 114688T) represents a novel species and strain OS3-89 (=KACC 19753=NBRC 114400) is a strain of A. litoris. On the basis of the data obtained here, strain OS3-83T is considered to represent a new species of the genus Actinomadura, for which the name Actinomadura terrae sp. nov. is proposed.


Asunto(s)
Actinomadura , Cactaceae , Ácidos Grasos/química , Fosfolípidos , ARN Ribosómico 16S/genética , Rizosfera , Filogenia , Microbiología del Suelo , ADN Bacteriano/genética , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana , Composición de Base
7.
Molecules ; 27(23)2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36500287

RESUMEN

Large scale cultivation and chemical investigation of an extract obtained from Actimonadura sp. resulted in the identification of six previously undescribed spirotetronates (pyrrolosporin B and decatromicins C-G; 7-12), along with six known congeners, namely decatromicins A-B (1-2), BE-45722B-D (3-5), and pyrrolosporin A (6). The chemical structures of compounds 1-12 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, Acinetobacter baumannii and Gram-positive bacteria, Staphylococcus aureus and were investigated for their cytotoxicity against the human cancer cell line A549. Of these, decatromicin B (2), BE-45722B (3), and pyrrolosporin B (7) exhibited potent antibacterial activities against both Gram-positive (MIC90 between 1-3 µM) and Gram-negative bacteria (MIC90 values ranging from 12-36 µM) with weak or no cytotoxic activity against A549 cells.


Asunto(s)
Policétidos , Humanos , Policétidos/química , Actinomadura , Antibacterianos/farmacología , Antibacterianos/química , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana
8.
J Antibiot (Tokyo) ; 75(10): 576-582, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36056265

RESUMEN

Nine new hydroxyphenyloxazolines, madurastatin B4, C2, D3 and D4, E1 and E2, F1 as well as G1 and G2 (8-16), along with two new enantiomers of madurastatin D1 (ent-6) and D2 (ent-7) and two known congeners, madurastatin B1 (2) and C1 (5), were isolated from the liquid culture of Actinomadura sp. ST100801 based on the initial activity against Escherichia coli screened in bicarbonate-supplemented Mueller Hinton II medium and identification via molecular networking. Structure elucidation was achieved by comprehensive 1D and 2D NMR as well as MS/MS fragmentation analyses. Their absolute configuration was determined by Marfey's analysis. Complemented with functionalized hydroxyphenyloxazolines (2, 4, 17-18) obtained by total synthesis, the isolated compounds were evaluated for antibacterial activities revealing MICs down to 4 µg ml-1 against Moraxella catarrhalis. Therefore, this study enlarges the family of madurastatin siderophores.


Asunto(s)
Actinomadura , Sideróforos , Antibacterianos/química , Escherichia coli , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Espectrometría de Masas en Tándem
9.
Artículo en Inglés | MEDLINE | ID: mdl-36001470

RESUMEN

A novel actinomycete strain, named LHW52907T, was isolated from a marine sponge (Leucetta chagosensis) collected in the South China Sea. The strain developed branched mycelia without fragmentation and short spore chains in hook-and- spiral form with wrinkled surfaces, bearing no more 10 spores. The cell-wall hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid. The sugars in whole-cell hydrolysates consisted of mannose, ribose, glucose, galactose and madurose. The major fatty acids of the strain were C16 : 0, C17 : 0 and C18 : 1 ω9c. The predominant menaquinone was MK-9(H6). The strain had the highest 16S rRNA gene sequence similarity of 99.72 % to Actinomadura pelletieri DSM 43383T. However, the average nucleotide identity and in silico DNA-DNA hybridization values between them were 93.6 and 52.6 %, respectively, readily distinguishing them as two different species. The results indicate that strain LHW52907T represents a novel species of the genus Actinomadura, for which we propose the name Actinomadura spongiicola sp. nov, with the type strain LHW52907T (=DSM 106571T=CGMCC 4.7596T).


Asunto(s)
Actinomadura , Poríferos , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfolípidos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/química
10.
Artículo en Inglés | MEDLINE | ID: mdl-35816443

RESUMEN

A novel actinomycete strain PM05-2T was isolated from the lichen Parmotrema praesorediosum (Nyl.) Hale collected from Chaiyaphum Province, Thailand. The taxonomic position of the strain was studied using the polyphasic approach. Based on the morphology and chemotaxonomic properties, strain PM05-2T was identified as a member of the genus Actinomadura. The whole-cell hydrolysate contained meso-diaminopimelic acid, rhamnose, ribose, xylose, madurose, glucose and galactose. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified phosphoglycolipid, four unidentified phospholipids and one unidentified lipid. The menaquinones were MK-9(H6), MK-9(H4), MK-9(H2), MK-9(H8) and MK-9(H0). The major cellular fatty acids were C16:0 and C18:1 ω9c. Strain PM05-2T showed the highest 16S rRNA gene similarity to Actinomadura hibisca NBRC 15177T (98.58%), Actinomadura kijaniata NBRC 14229T (98.29 %) and Actinomadura namibiensis DSM 44197T (98.14 %). The phylogenetic tree analysis revealed that strain PM05-2T was related to A. hibisca NBRC 15177T, A. kijaniata NBRC 14229T, A. namibiensis DSM 44197T and Actinomadura macrotermitis RB68T. The genomic analysis revealed that average nucleotide identity values based on both blast and MUMmer between strain PM05-2T and the relative type strains ranged from 77.6 to 86.4%. The digital DNA-DNA hybridization values among the strains were lower than the threshold for assigning to the same species. The taxonomic results suggested that strain PM05-2T represented a novel species of the genus Actinomadura for which the name Actinomadura parmotrematis is proposed. The type strain is PM05-2T (=TBRC 15492T=NBRC 115416T).


Asunto(s)
Actinomycetales , Líquenes , Actinomadura , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Parmeliaceae , Fosfolípidos/análisis , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Microbiología del Suelo , Vitamina K 2
11.
Chemistry ; 28(36): e202200612, 2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35404539

RESUMEN

In this study, we analyzed if Actinomadura sp. RB99 produces siderophores that that could be responsible for the antimicrobial activity observed in co-cultivation studies. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and global natural product social molecular networking platform (GNPS) analysis of fungus-bacterium co-cultures resulted in the identification of five madurastatin derivatives (A1, A2, E1, F, and G1), of which were four new derivatives. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, as well as MS/MS data and their absolute structures were elucidated based on Marfey's analysis, DP4+ probability calculation and total synthesis. Structure analysis revealed that madurastatin E1 (2) contained a rare 4-imidazolidinone cyclic moiety and madurastatin A1 (5) was characterized as a Ga3+ -complex. The function of madurastatins as siderophores was evaluated using the fungal pathogen Cryptococcus neoformans as model organism. Based on homology models, we identified the putative NRPS-based gene cluster region of the siderophores in Actinomadura sp. RB99.


Asunto(s)
Isópteros , Sideróforos , Actinomadura , Animales , Isópteros/microbiología , Espectroscopía de Resonancia Magnética , Sideróforos/química , Espectrometría de Masas en Tándem
12.
J Nat Prod ; 85(4): 1098-1108, 2022 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-35343685

RESUMEN

Chemical investigation of the fermentation products of a deep sea water-derived actinomycete, Actinomadura sp. KD439, identified seven new angucyclinones, designated as kumemicinones A-G (1-7), together with the known SF2315B and miaosporone E. NMR and MS spectroscopic analyses, combined with X-ray crystallography and quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) spectra, uncovered the structures of new angucyclinones as regioisomers of SF2315B at the allyl alcohol unit (1 and 2), an epoxy ring-opened γ-hydroxy enone isomer (3), a B/C-ring-rearranged product (4), or dimers with a new mode of bridging (5-7), adding new structural variation to this antibiotic group. The absolute configuration of SF2315B was also determined by comparison of ECD spectra with those of 1 and 2. All the angucyclinones exhibited cytotoxicity against P388 murine leukemia cells, with IC50 values ranging from 1.8 to 53 µM.


Asunto(s)
Actinobacteria , Antineoplásicos , Actinomadura , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular
13.
J Dermatolog Treat ; 33(2): 954-958, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32643472

RESUMEN

BACKGROUND: Actinomycetoma due to Actinomadura madurae is susceptible to numerous chemotherapeutic agents, however, the response to those treatments is variable and closely related to several factors. OBJECTIVE: We aimed to evaluate the clinical-therapeutic characteristics of patients with actinomycetoma due to Actinomadura madurae with two treatment modalities. METHODS: This was a retrospective study of eighteen patients with a diagnosis of actinomycetoma. The most widely used therapeutic scheme was streptomycin 1 g every third day plus TMP/SMX 800 mg/160 mg/12h, followed by TMP/SMX with DDS 100 mg/day. In six patients (33%), ciprofloxacin 500 mg every 12 h was used instead of DDS. RESULTS: Conventional scheme achieved clinical and mycological cure in 58% of the cases, improvement in 16%, and 25% of the patients failed to treatment; in the cases treated with ciprofloxacin, clinical and microbiological cure was achieved in 83% of patients and clinical improvement in 16%. The treatment time to achieve clinical and mycological did not have a statistically significant difference (median 10 ± 1.38 vs. 12 ± 4.6). CONCLUSION: Treatment based on streptomycin + TMP/SMX with ciprofloxacin was found to be effective in treating patients with actinomycetoma, and comparable to the conventional treatment with DDS in actinomycetoma due to A. madurae with minimal bone involvement.


Asunto(s)
Micetoma , Actinomadura , Humanos , Micetoma/diagnóstico , Micetoma/tratamiento farmacológico , Micetoma/microbiología , Estudios Retrospectivos , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico
14.
Int J Syst Evol Microbiol ; 71(12)2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34870574

RESUMEN

An actinomycete strain, LCR2-06T, isolated from a lichen sample on rock collected from Chiang Rai Province (Pong Phra Bat Waterfall), Thailand, was characterized using a polyphasic approach. The strain grew at 25-45 °C, pH 6-11 and on International Streptomyces Project 2 agar plate with 5 % (w/v) NaCl. It contained meso-diaminopimelic acid as the diamino acid in whole-cell hydrolysates. Rhamnose, ribose, xylose, madurose, glucose and galactose were detected as whole-cell sugar hydrolysates. Mycolic acids were absent. The N-acyl type of muramic acid was acetyl. The strain contained C16 : 0, TBSA 10-methyl C18 : 0 and 2-hydroxy C16 : 0 as the predominant fatty acids and MK-9(H6), MK-9(H4) and MK-9(H8) as the major menaquinones. The major polar lipids were diphosphatidylglycerol, phosphatidylinositol and unidentified phospholipid. The draft genome of strain LCR2-06T was closely related to Actinomadura barringtoniae TBRC 7225T (99.2 %), Actinomadura nitritigenes NBRC 15918T (98.8 %), Actinomadura montaniterrae TISTR 2400T (98.5 %) and Actinomadura physcomitrii JCM 33455T (97.9 %). The draft genome of LCR2-06T was 11.1 Mb with 10 588 coding sequences with an average G+C content of 72.7 mol%. Results of genomic analysis revealed that the ANIb and ANIm values between strain LCR2-06T and A. montaniterrae TISTR 2400T were 90.0 and 92.0 %, respectively. The digital DNA-DNA hybridization value was 43.9 % in comparison with the draft genome of A. montaniterrae TISTR 2400T. The strain produced an antibacterial compound active against Bacillus subtilis ATCC 6633 and Kocuria rhizophila ATCC 9341. The results of taxonomic analysis suggested that strain LCR2-06T represented a novel species of the genus Actinomadura for which the name Actinomadura violacea sp. nov. is proposed. The type strain is LCR2-06T (=JCM 33065T=KCTC 49547T=NBRC 114810T=LMG 32136T=TISTR 2935T).


Asunto(s)
Actinomadura/clasificación , Líquenes , Oligopéptidos/biosíntesis , Filogenia , Actinomadura/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Líquenes/microbiología , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Tailandia , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
Acta Chim Slov ; 68(3): 575-586, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34897543

RESUMEN

This work mainly focused on the production of an efficient, economical, and eco-friendly lipase (AKL29) from Actinomadura keratinilytica strain Cpt29 isolated from poultry compost in north east of Algeria, for use in detergent industries. AKL29 shows a significant lipase activity (45 U/mL) towards hydrolyzed triacylglycerols, indicating that it is a true lipase. For maximum lipase production the modeling and optimization of potential culture parameters such as incubation temperature, cultivation time, and Tween 80 (v/v) were built using RSM and ANN approaches. The results show that both the two models provided good quality predictions, yet the ANN showed a clear superiority over RSM for both data fitting and estimation capabilities. A 4.1-fold increase in lipase production was recorded under the following optimal condition: incubation temperature (37.9 °C), cultivation time (111 h), and Tween 80 (3.27%, v/v). Furthermore, the partially purified lipase showed good stability, high compatibility, and significant wash performance with various commercial laundry detergents, making this novel lipase a promising potential candidate for detergent industries.


Asunto(s)
Actinomadura/enzimología , Proteínas Bacterianas/química , Detergentes/química , Lipasa/química , Proteínas Bacterianas/aislamiento & purificación , Estabilidad de Enzimas , Proteínas Fúngicas/química , Cinética , Lipasa/aislamiento & purificación , Redes Neurales de la Computación , Saccharomycetales/enzimología , Triglicéridos/química
16.
J Nat Prod ; 84(11): 2775-2785, 2021 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-34748348

RESUMEN

Eight new angucyclic quinones, miaosporones A to H (1-8), along with the previously described metabolites 8-hydroxy-3-methylbenz[a]anthraquinone (9), tetrangulol (10), 5,6-dihydro-1,8-dihydroxy-3-methybenz[a]anthracene-7,12-quinone (11), and SF2315A (12), were isolated from the terrestrial actinomycete Actinomadura miaoliensis TBRC 5172 obtained from sediment collected from the Huai Yang reservoir, Prachuap Khiri Khan Province, Thailand. The relative and absolute configurations of the new compounds were determined from analysis of NMR spectroscopic and X-ray crystallographic data. Miaosporone A exhibited antimalarial activity against Plasmodium falciparum K1 and antibacterial activity against Mycobacterium tuberculosis with respective IC50 values of 2.5 and 2.4 µM and displayed cytotoxic activities against both cancerous (MCF-7 and NCI-H187) and nonmalignant (Vero) cells.


Asunto(s)
Actinomadura/metabolismo , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Quinolonas/aislamiento & purificación , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Espectroscopía de Resonancia Magnética , Mycobacterium tuberculosis/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Quinolonas/química , Quinolonas/farmacología
17.
PLoS One ; 16(11): e0260413, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34847153

RESUMEN

As part of a screening programme for antibiotic-producing bacteria, a novel Actinomadura species was discovered from a soil sample collected in Santorini, Greece. Preliminary 16S rRNA gene sequence comparisons highlighted Actinomadura macra as the most similar characterised species. However, whole-genome sequencing revealed an average nucleotide identity (ANI) value of 89% with A. macra, the highest among related species. Further phenotypic and chemotaxonomic analyses confirmed that the isolate represents a previously uncharacterised species in the genus Actinomadura, for which the name Actinomadura graeca sp. nov. is proposed (type strain 32-07T). The G+C content of A. graeca 32-07 is 72.36%. The cell wall contains DL-diaminopimelic acid, intracellular sugars are glucose, ribose and galactose, the predominant menaquinone is MK-9(H6), the major cellular lipid is phosphatidylinositol and fatty acids consist mainly of hexadecanoic acid. No mycolic acid was detected. Furthermore, A. graeca 32-07 has been confirmed as a novel producer of the non-ribosomal peptide antibiotic zelkovamycin and we report herein a provisional description of the unique biosynthetic gene cluster.


Asunto(s)
Actinomadura , Péptidos Catiónicos Antimicrobianos , Composición de Base , Compuestos Macrocíclicos/metabolismo , Actinomadura/clasificación , Actinomadura/genética , Actinomadura/metabolismo , Actinomadura/ultraestructura , Péptidos Catiónicos Antimicrobianos/biosíntesis , Péptidos Catiónicos Antimicrobianos/genética
18.
Int J Syst Evol Microbiol ; 71(10)2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34705623

RESUMEN

An actinobacterium, designated 14C53T, was isolated from a soil sample on basaltic material from Samsun, Turkey. The growth ranges for NaCl concentration and pH of strain 14C53T were quite limited and the growth temperature range of the strain was 20-37 °C, with an optimum at 28 °C. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain 14C53T was most closely related to Actinomadura geliboluensis A8036T (98.5 % similarity value), but in the phylogenetic tree, it formed a clade with Actinomadura alkaliterrae D310AT. The genome tree revealed a close relationship between the strain and Actinomadura pelletieri DSM 43383T. However, the digital DNA-DNA hybridization and average nucleotide identity values between strain 14C53T with Actinomadura geliboluensis A8036T and Actinomadura pelletieri DSM 43383T were 28.6-30.2 % and 84.3-85.5 %, respectively, and comparative analyses based on the genome sequences demonstrated that it represents a novel species of the genus Actinomadura. The genome size of strain 14C53T was approximately 9.0 Mb and the genomic DNA G+C content of the strain was 71.3 mol%. The major cellular fatty acids of strain 14C53T were C16 : 0 and iso-C16 : 0. Strain 14C53T contained meso-diaminopimelic acid as the diamino acid in the cell-wall peptidoglycan. The predominant menaquinones were MK-9(H8) and MK-9(H6). Based on evidence collected from the phenotypic, genotypic and phylogenetic analyses, a novel species Actinomadura soli sp. nov. is proposed, with 14C53T (=DSM 104447T=KCTC 39878T) as the type strain.


Asunto(s)
Actinomadura/clasificación , Filogenia , Microbiología del Suelo , Actinomadura/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Turquía , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Molecules ; 26(13)2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34209118

RESUMEN

Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.


Asunto(s)
Actinomadura/crecimiento & desarrollo , Madurella/crecimiento & desarrollo , Micetoma , Niclosamida/farmacología , Animales , Humanos , Micetoma/tratamiento farmacológico , Micetoma/microbiología
20.
Antonie Van Leeuwenhoek ; 114(2): 195-208, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33449222

RESUMEN

Isolation of novel actinobacteria from unexplored habitats as potential sources of novel drug leads has utmost importance. During the course of screening arid soil samples for novel actinobacteria, strain H3C3T was isolated from Malatya, Turkey and its taxonomic position was revealed by a genome-based polyphasic approach. Pairwise sequence comparison of the 16S rRNA gene showed that the strain is closely related to Actinomadura fibrosa JCM 9371T with sequence identity level of 99.0%. Comparative genome analyses based on digital DNA-DNA hybridization and average nucleotide identity indicated that strain H3C3T represents a novel species within the genus Actinomadura. The strain has typical characteristics of the genus Actinomadura, i.e. meso-diaminopimelic acid as diagnostic amino acid; galactose, glucose, madurose and ribose as whole-cell sugars. Major menaquinones detected were MK-9(H6), MK-9(H8) and polar lipids were diphosphatidylglycerol, phosphatidylinositol, glycophospholipid and unknown phospholipid and lipids. Its genome size is approximately 10.2 Mb with G+C content of 71.6%. Further genomic analyses of strain H3C3T indicated its high potential for novel biosynthetic gene clusters coding for various chemical structures. On the basis of phenotypic and phylogenetic analyses, strain H3C3T represents a novel species of the genus Actinomadura, for which Actinomadura rubrisoli sp. nov. is proposed, and it holds high promise for novel biosynthetic metabolites of value to biopharmaceutical industry.


Asunto(s)
Actinobacteria , Actinomadura , Actinobacteria/genética , Técnicas de Tipificación Bacteriana , Pared Celular/química , ADN Bacteriano/genética , Ácidos Grasos/análisis , Genómica , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Microbiología del Suelo , Vitamina K 2
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