There are several well-studied examples of protective symbiosis between insect-host and symbiotic actinobacteria, producing antimicrobial metabolites to inhibit host pathogens. These mutualistic relationships are best described for some wasps and leaf-cutting ants while a huge variety of insect species still remains poorly explored. For the first time we isolated actinobacteria from harvester ant Messor structor, and evaluated the isolates’ potential as antimicrobial producers. All isolates could be divided into two morphotypes of single and mycelial cells. We found that the highest frequency of occurrence of mycelial morphotype was observed among soldiers, and the lowest among larvae in the studied laboratory colony. The representative of this morphotype was identified as Streptomyces globisporus subsp. globisporus 4-3 by polyphasic approach. It was established using E. coli JW5503 pDualRep2 system, that crude broths of mycelial isolates inhibited a protein synthesis in reporter strains, but it did not disrupt the in vitro synthesis of proteins in cell-free extracts. Active compound was extracted, purified and identified as albomycin δ2. Pronounced ability of albomycin to inhibit the growth of entomopathogens suggests that Streptomyces globisporus subsp. globisporus may be involved in defensive symbiosis with the Messor structor ant against infections.

A replicated outdoor pot experiment was conducted in order to investigate the effect of different phytohormone and siderophore producing, and P-solubilizing bacterial species on spinach nu-trient uptake, nitrate concentration and nitrate reductase activity. The mentioned parameters were determined in spinach leaves (Spinacia oleracea L.), non-inoculated and inoculated with four plant growth–promoting actinobacteria (Streptomyces griseus (S1), Streptomyces albogriseolus (S2), Strep-tomyces aurantiacus (S3) and Streptomyces kanamyceticus (S4) under the influence of two sources of nitrogen fertilizers including potassium nitrate and urea (100 and 200 ppm). Inoculation with the strains increased spinach shoot fresh weight by 16%–43% over the control. Bacterial inoculation gave leaf chlorophyll increases of 15%–40%. Inoculation increased plant height by 2.2%–24.6% in spinach. A close reverse relationship between nitrate concentration and enzyme activity (r2= 0.87) was demonstrated. The measured parameter responses were variable and dependent on the in-oculant strain, with highest enzyme activity and lowest nitrate concentration exhibited in S2 (S. albogriseolus) inoculation. The source and application dose of nitrogen fertilizer had varied impact on measured parameter. The maximum phosphorous and iron concentration were measured by soil inoculation with S4 and applying 200 ppm nitrate potassium nitrogen fertilizer. Application of 200 ppm KNO3 nitrogen fertilizer with different Streptomyces strains showed the capability of S2 in decreasing nitrate content while protein content increased. In particular, the strains S2 and S4 have great potential in being formulated and used as biofertilizers.

Four angucycline glycosides including three new compounds landomycin N (1), galtamycin C (2) and vineomycin D (3), and a known homologue saquayamycin B (4), along with two alkaloids 1-acetyl-β-carboline (5) and indole-3-acetic acid (6), were identified from the fermentation broth of an intertidal sediments derived Streptomyces sp. Their structures were mainly established by IR, HR-ESI-MS, 1D and 2D NMR techniques. Among the isolated angucyclines, saquayamycin B displayed potent cytotoxic activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5, with IC50 values 0.135, 0.033 and 0.244 μM respectively, superior to positive drug doxorubicin. Saquayamycin B treatment to SMMC-7721 cells led to the typical morphological signs of apoptosis in 4',6-diamidino-2-phenylindole (DAPI) staining experiment.

Natural alkaloids of actinomycetes origin and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids since more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activity, etc. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided.

A large number of studies have indicated that plant community modulate the yield, improve growth and promote development of host plants, and among them rhizosphere growth-promoting bacteria play an important role in increasing crop yield. Bacteria benefit from the plant nutrients provided by the roots, but plants can benefit from their rhizobacteria as well. Rhizobia are considered as the most important candidate for plant growth promotion in comparison with rhizobacteria due to their endophytic nature and nitrogen fixing ability. They can also provide auxins which play a notable function in plant growth and plant-microbe interactions. Bacillus spp., the sporulating Gram-positive bacteria, have important roles in plant growth promotion and induction of systemic resistance. Pseudomonas are Gram-negative aerobic chemoheterotroph and are usually found in the environment. Streptomyces are important groups of soil bacteria from the actinomycetes family. Most of them are efficient rhizosphere and rhizoplane colonizers, and they can also be endophytes colonizing inner tissues of host plants. The present review aims to present the most up-to-date findings and results regarding the effects of plant growth promoting bacteria on yield of different crops, especially sorghum. Furthermore, the mechanisms of the actions of different bacteria briefly illustrated, aiming to present future needs to be addressed in sustainable crop production. Plant growth promoting rhizobacteria inoculation with different plants or treating plants with microbe-to-plant signal constituents can be an effectual technique to stimulate crop growth. They are also active in protecting crops from phytopathogens and environmental stress, plant pathogens and they have positive roles in nutrient cycling.

Dengue has long been a serious health burden to the global community, especially for those living in the tropics. In spite of the availability of vaccines, effective treatment for the infection is still needed and currently remained absent. In the present study, antiviral properties of the KSF 103 ME which consisted of a number of potential antiviral compounds were investigated against DENV-2. The effects of this extract against DENV-2 replication were determined using the qRT-PCR. Findings from the study suggested that the KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively) and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively. The KSF 103 ME inhibited dengue virus repication with an IC50 value of 20.3 µg/mL and SI value of 38.9. The KSF 103 ME showed potent antiviral properties against DENV during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the KSF 103 ME against DENV.

Polyketides are large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces that responsible for producing polyketides. This paper focuses on biosynthesis of polyketides in Streptomyces with three structurally different types of PKSs.

The aim of this work is the study of genome organization and metabolic potential of Streptomyces carpaticus strain SCPM-O-B-9993, promising plant-protecting and plant-stimulating strain isolated from brown semi-desert soils with a very high degree of salinity. The genome of the strain contains of a linear chromosome of 5,968,715 bp and has no plasmids. Gene clusters of production of secondary metabolites with antimicrobial properties (ohmyungsamycin, pellasoren, naringenin, ansamycin) were identified in the genome. The strain SCPM-O-B-9993 has antiviral activity against cucumber mosaic virus on tomatoes under laboratory conditions.

Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. However, a sufficient therapeutic drug was not developed yet. Caboxamycin, a benzoxazole antibiotic, isolated from the culture broth of the marine strain Streptomyces sp., SC0774, displayed an antiviral effect in the CVB3-infected HeLa cells and CVB3-induced myocarditis mouse model. Caboxamycin significantly inhibited CVB3 VP1 production and cleavage of translation factor eIF4G1 from CVB3-infected HeLa cells at a 100 μg/ml concentration. Moreover, virus RNA amplification was dramatically reduced by caboxamycin treatment in HeLa cells. The caboxamycin cardiac protective effect was observed on the CVB3-mediated myocarditis mice model. The caboxamycin-treated mice survival was significantly increased compared to untreated mice (treated vs untreated, 100 vs 45 %). Heart histologic findings showed that myocardium damage and inflammation were significantly decreased by caboxamycin treatment. Caboxamycin directly inhibited caspase3 activity and cardiac myocytes apoptosis. These results suggested that caboxamycin strongly suppressed cardiac myocyte apoptosis and effectively inhibited the proliferation of CVB3 from in vitro and in vivo conditions. Furthermore, this study proposed that caboxamycin could potentially be applied in developing a new antiviral drug for CVB3-induced myocarditis.

In their natural environment, bacteria are exposed to various stresses. The stress-response sigma factor SigB of gram-positive Bacillus subtilis is the best-characterized example. Unlike Bacillus subtilis, the gram-positive bacterium Streptomyces coelicolor A3(2) contains nine SigB homologues (SigBFGHIKLMN) with a major role in differentiation and response to osmotic stress. We previously constructed a two-plasmid system to identify promoters recognized by these sigma factors. Interestingly, almost all identified promoters were recognized by two or more SigB homologues. However, no specific sequences characteristic for these recognition groups were found. To examine this cross-recognition in vivo in S. coelicolor A3 (2), one of these promoters was cho-sen, which drives the expression of the sporulation-specific gene ssgB. The ssgBp promoter was inserted into a luciferase reporter plasmid and conjugated to S. coelicolor M145 and nine mutant strains containing deleted individual sigB homologous genes. Luciferase reporter activity indi-cated differential activity of this promoter in these mutant strains, suggesting overlapping pro-moter recognition by these SigB homologues. To determine which nucleotides in the ̶ 10 re-gion are responsible for the selection of a specific SigB homologue, several mutant promoters with altered last three nucleotides in this region were prepared and tested in the two-plasmid system. Some mutant promoters were specifically recognized by some SigB homologues. Mutant promoters were inserted into a luciferase reporter plasmid and conjugated to S. coelicolor A3(2) and these nine mutant strains. Luciferase reporter activity indicated differential activity of these ssgBp mutant promoters, indicating overlapping promoter recognition by these SigB homologues in S. coelicolor A3(2).

Damping-off caused by Pythium aphanidermatum (Pa) is one of the most destructive diseases for watemelon seedlings. Application of biological control agents against Pa has attracted attention of many researchers for a long time. In this study, an actinomycete isolate JKTJ-3 with strong and broad-spectrum antifungal effect was screened from 23 bacterial isolates. Based on the morphological, cultural, physiological, and biochemical characteristics as well as the feature of 16S rDNA sequence, isolate JKTJ-3 was identified as Streptomyces murinus. We compared the biocontrol efficacy of isolate JKTJ-3 and its metabolites. The results revealed that seed and substrate treatments with the JKTJ-3 cultures showed a significant inhibitory effect on watermelon damping-off disease. Seed treatment with the JKTJ-3 cultural filtrates (CF) had higher control efficacy that of the fermentation cultures (FC). Treatment of the seeding substrate with the wheat grain cultures (WGC) of JKTJ-3 exhibited better control efficacy than that of the seeding substrate with the JKTJ-3 CF. Moreover, the JKTJ-3 WGC showed the preventive effect on suppression of the disease, and the efficacy increased with increase in the inoculation interval between the WGC and Pa. Production of the antifungal metabolite actinomycin D by isolate JKTJ-3 and cell wall-degrading enzymmes such as β-1,3-glucanase and chitosanase was probably the mechanisms for effective control of watermelon damping-off. It was showed for the first time that S. murinus can produce anti-oomycete substances including chitinase and actinomycin D. This is the first report about S. murinus used as biocontrol agent against watermelon Pa-induced damping-off.

Microbe-plant interactions are linked with the core microbiota, and both the plant and the microbial partners depend on one other to thrive in nature. However, why and how the below-ground core microbiota become established aboveground is poorly understood. We tracked the movement of a probiotic Streptomyces endophyte throughout a managed strawberry ecosystem. Probiotics in the rhizosphere and anthosphere were genetically identical, yet these niches were segregated in space and time. The probiotic in the rhizosphere moved upward via the vascular bundle, relocated to aboveground plant parts, and protected against Botrytis cinerea. It also moved from flowers to roots, and among flowers via pollinators that were protected against pollinator pathogens. Our results reveal a solid evidence in tripartite interaction with Streptomyces exploiting plant and pollinator partners.

Lathyrane-type diterpenes have a wide range of biological activities. Among them, euphoboetirane A (1) exerts neurogenesis-promoting activity. In order to increase the structural diversity of this type of lathyranes to explore their potential use in neurodegenerative disorders, the biotransformation of 1 by Streptomyces puniceus BC-5GB.11 has been investigated. The strain BC-5GB.11, isolated from surface sediments collected from the intertidal zone of the inner Bay of Cadiz, was identified as Streptomyces puniceus, as determined by phylogenetic analysis using 16S rRNA gene sequence. Biotransformation of 1 by BC-5GB.11 afforded five products (3-7), all of them reported here for the first time. The main biotransformation pathways involved regioselective oxidation at non-activated carbons (3-5) and isomerization of the D^12,13 double bond (6). In addition, a cyclopropane-rearranged compound was found (7). The structures of all compounds were elucidated on the basis of extensive NMR and HRESIMS spectroscopic studies.

Moonmilk are cave carbonate deposits that host a rich microbiome including antibiotic-producing Actinobacteria making these speleothems appealing for bioprospecting. Here we investigated the taxonomic profile of the actinobacterial community of three moonmilk deposits of the cave “Grotte des Collemboles” via high-throughput sequencing of 16S rRNA amplicons. Actinobacteria was the most common phylum after Proteobacteria, ranging from 9 to 23% of the total bacterial population. Next to actinobacterial OTUs attributed to uncultured organisms at the genus level (~44%), we identified 47 actinobacterial genera with Rhodoccocus (4 OTUs, 17%) and Pseudonocardia (9 OTUs, ~16%) as the most abundant in terms of absolute number of sequences. Streptomycetes presented the highest diversity (19 OTUs, 3%), with most of OTUs unlinked to the culturable Streptomyces strains previously isolated from the same deposits. 43% of OTUs were shared between the three studied collection points while 34% were exclusive to one deposit indicating that distinct speleothems host their own population despite their nearby localization. This important spatial diversity suggests that prospecting within different moonmilk deposits should result in the isolation of unique and novel Actinobacteria. These speleothems also host a wide range of non-streptomycetes antibiotic-producing genera, and should therefore be subjected to methodologies for isolating rare Actinobacteria.

This study aims to explore the potential inhibition effects of staurosporine isolated from a Strepto-myces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimi-crobial and antihypertensive activities. This research focuses on investigating the effects of stau-rosporine on suppressing the growth and development of nasal polyps and elucidating the un-derlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF- β1 in the presence of staurosporine. The levels of -smooth muscle actin (-SMA), collagen type-I (Col-1), fibronectin, and phosphory-lated (p)-Smad 2 were investigated using western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-β1 stimulated the production of Col-1, fibronectin, and -SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-β1-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine’s role in nasal polyp management and provide insights into its mechanisms of action.

Plant pathogenic fungi are the most important cause of losses in agriculture. In the face of the overuse of synthetic fungicides, natural products are an encouraging alternative to control these plant pathogenic fungi. In this study, we tested the antifungal capacity of metabolites produced by strains of the genus Streptomyces against the plant pathogenic fungi Alternaria alternata, Botrytis cinerea and Fusarium oxysporum. In addition, we investigated the feasibility of applying these metabolites in a postharvest setting for the control of B. cinerea on cherry tomato fruits. The results revealed the ability of the strains, especially Streptomyces netropsis, to inhibit the growth of plant pathogenic fungi and, in some cases, the sporulation of these fungi. In addition, we observed an interesting phenomenon in which Streptomyces strains physically encapsulated the mycelium of the fungi, which contributed to their inhibition. Finally, the protective activity of S. netropsis extract on Cherry tomato fruits infected with B. cinerea was demonstrated. In conclusion, this research opens the door to studies on the understanding of physical microbial interactions in natural environments and holds promise in agriculture, especially in the protection of agricultural products during the post-harvest stage as a safer and more sustainable alternative.

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 3-copy gul-integration strains S. coelicolor M1346::3gul showed better production than one-copy or 2-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 were reported to 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 provided important clues for future studies on enhancing antibiotic production in Streptomyces systems.

Banana wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is a devastating fungal disease. Biocontrol strategies owned immense potential in inhibiting the spread of Foc TR4. Here, thirty actinobacteria were isolated from soils and screened for their antagonistic activity against Foc TR4. Strain SCA4-21T exhibited broad-spectrum antifungal activity against nine phytopathogenic fungi including Foc TR4. The strain was identified as the genus Streptomyces according to phenotypic characteristics and 16S rRNA gene phylogenetic analysis. Multi-locus sequence analysis based on five house-keeping gene alleles (atpD, gyrB, recA, rpoB, and trpB) revealed that strain SCA4-21T clustered into S. hygroscopicus subsp. hygroscopicus NBRC 13472T with 100% of bootstrap value. Average nucleotide identity and dDDH were 98.49% and 44.30% above the threshold of novel species. Hence, strain SCA 4-21T represented a novel species within the genus Streptomyces, named as Streptomyces luomodiensis sp. nov.. The type strain is SCA4-21T (=GDMCC4.340T= JCM36555T). By the CAZymes analysis, 348 carbohydrate-active enzymes were detected, including 15 chitinases and 8 β-1,3-glucanases. The fermentation broth of strain SCA4-21T showed high activities of chitinase and β-1,3-glucanase, contributing to the antifungal activity. Our results showed an innovative potential biocontrol agent for managing plant fungal diseases, specifically banana fusarium wilt.