Actinobacteria and Myxobacteria—Important Resources for Novel Antibiotics 2.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 50245

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Working Group Microbial Strain Collection, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, D-38124 Braunschweig, Germany
Interests: polyphasic taxonomy; cultivation methods; isolation methods; taxonomy and secondary metabolites from Actinobacteria and Myxobacteria; morphology and fine structure of Actinobacteria and Myxobacteria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bacterial infections cause millions of deaths globally, particularly in children and the elderly, and four of the 10 leading causes of death are infectious diseases in low- and middle-income countries. The continuous use of antibiotics has resulted in multi-resistant bacterial strains all over the world, such as Community-associated Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamases (ESBLs), and, as expected, hospitals have become breeding grounds for human-associated microorganisms, especially in critical care units.

Natural products are the bedrock and a valuable source for drug discovery programs. More than 60% of the drugs that are available on the market are derived from natural sources. Many antibiotics are made chemically via modification of natural products through a process called semi synthesis. Natural product structures have the characteristics of a high chemical diversity, biochemical specificity, and high binding affinities to their specific receptor and also interact with a wide variety of biological targets.

Microorganisms produce a wide range of natural products, which are used as lead components in the drug discovery era. Over 6000 compounds of microbial origin with anti-microbial activities have been isolated. The microbial world represents 90% of all biological diversity and less than 1% has presently been explored (Molinari 2009). Mining microbial diversity is the key to obtaining high compound diversity, because a very large source for new natural products remains unexplored. To date, a few groups of microorganisms have been known to be high and potent producers of natural products: Actinomycetes, Bacillus, cyanobacteria, fungi and myxobacteria.

Dr. Joachim Wink
Guest Editor

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Keywords

  • Polyphasic Taxonomy
  • Secondary Metabolites
  • Biotechnology
  • Differentiation
  • Biosynthesis
  • Morphology
  • PKS and NRPS

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Editorial

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3 pages, 172 KiB  
Editorial
Special Issue: “Actinobacteria and Myxobacteria—Important Resources for Novel Antibiotics”
by Joachim Wink
Microorganisms 2020, 8(10), 1464; https://doi.org/10.3390/microorganisms8101464 - 24 Sep 2020
Cited by 1 | Viewed by 1717
Abstract
The history of our antibiotics is inseparably connected to microorganisms as producers [...] Full article

Research

Jump to: Editorial, Review

19 pages, 3380 KiB  
Article
Isolation and Characterization of a New Endophytic Actinobacterium Streptomyces californicus Strain ADR1 as a Promising Source of Anti-Bacterial, Anti-Biofilm and Antioxidant Metabolites
by Radha Singh and Ashok K. Dubey
Microorganisms 2020, 8(6), 929; https://doi.org/10.3390/microorganisms8060929 - 19 Jun 2020
Cited by 34 | Viewed by 4685
Abstract
In view of the fast depleting armamentarium of drugs against significant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA) and others due to rapidly emerging drug-resistance, the discovery and development of new drugs need urgent action. In this endeavor, a new strain of endophytic actinobacterium [...] Read more.
In view of the fast depleting armamentarium of drugs against significant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA) and others due to rapidly emerging drug-resistance, the discovery and development of new drugs need urgent action. In this endeavor, a new strain of endophytic actinobacterium was isolated from the plant Datura metel, which produced secondary metabolites with potent anti-infective activities. The isolate was identified as Streptomyces californicus strain ADR1 based on 16S rRNA gene sequence analysis. Metabolites produced by the isolate had been investigated for their antibacterial attributes against important pathogens: S. aureus, MRSA, S. epidermis, Enterococcus faecium and E. faecalis. Minimum inhibitory concentration (MIC90) values against these pathogens varied from 0.23 ± 0.01 to 5.68 ± 0.20 μg/mL. The metabolites inhibited biofilm formation by the strains of S. aureus and MRSA (Biofilm inhibitory concentration [BIC90] values: 0.74 ± 0.08–4.92 ± 0.49 μg/mL). The BIC90 values increased in the case of pre-formed biofilms. Additionally, the metabolites possessed good antioxidant properties, with an inhibitory concentration (IC90) value of 217.24 ± 6.77 µg/mL for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging. An insight into different classes of compounds produced by the strain ADR1 was obtained by chemical profiling and GC-MS analysis, wherein several therapeutic classes, for example, alkaloids, phenolics, terpenes, terpenoids and glycosides, were discovered. Full article
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18 pages, 2554 KiB  
Article
Taxonomic Characterization and Secondary Metabolite Analysis of NEAU-wh3-1: An Embleya Strain with Antitumor and Antibacterial Activity
by Han Wang, Tianyu Sun, Wenshuai Song, Xiaowei Guo, Peng Cao, Xi Xu, Yue Shen and Junwei Zhao
Microorganisms 2020, 8(3), 441; https://doi.org/10.3390/microorganisms8030441 - 20 Mar 2020
Cited by 4 | Viewed by 2685
Abstract
Cancer is a serious threat to human health. With the increasing resistance to known drugs, it is still urgent to find new drugs or pro-drugs with anti-tumor effects. Natural products produced by microorganisms have played an important role in the history of drug [...] Read more.
Cancer is a serious threat to human health. With the increasing resistance to known drugs, it is still urgent to find new drugs or pro-drugs with anti-tumor effects. Natural products produced by microorganisms have played an important role in the history of drug discovery, particularly in the anticancer and anti-infective areas. The plant rhizosphere ecosystem is a rich resource for the discovery of actinomycetes with potential applications in pharmaceutical science, especially Streptomyces. We screened Streptomyces-like strains from the rhizosphere soil of wheat (Triticum aestivum L.) in Hebei province, China, and thirty-nine strains were obtained. Among them, the extracts of 14 isolates inhibited the growth of colon tumor cell line HCT-116. Strain NEAU-wh-3-1 exhibited better inhibitory activity, and its active ingredients were further studied. Then, 16S rRNA gene sequence similarity studies showed that strain NEAU-wh3-1 with high sequence similarities to Embleya scabrispora DSM 41855T (99.65%), Embleya hyalina MB891-A1T (99.45%), and Streptomyces lasii 5H-CA11T (98.62%). Moreover, multilocus sequence analysis based on the five other house-keeping genes (atpD, gyrB, rpoB, recA, and trpB) and polyphasic taxonomic approach comprising chemotaxonomic, phylogenetic, morphological, and physiological characterization indicated that the isolate should be assigned to the genus Embleya and was different from its closely related strains, therefore, it is proposed that strain NEAU-wh3-1 may be classified as representatives of a novel species of the genus Embleya. Furthermore, active substances in the fermentation broth of strain NEAU-wh-3-1 were isolated by bioassay-guided analysis and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. Consequently, one new Zincophorin analogue together with seven known compounds was detected. The new compound showed highest antitumor activity against three human cell lines with the 50% inhibition (IC50) values of 8.8–11.6 μg/mL and good antibacterial activity against four pathogenic bacteria, the other known compounds also exhibit certain biological activity. Full article
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15 pages, 1277 KiB  
Article
A Streptomyces sp. NEAU-HV9: Isolation, Identification, and Potential as a Biocontrol Agent against Ralstonia solanacearum of Tomato Plants
by Ling Ling, Xiaoyang Han, Xiao Li, Xue Zhang, Han Wang, Lida Zhang, Peng Cao, Yutong Wu, Xiangjing Wang, Junwei Zhao and Wensheng Xiang
Microorganisms 2020, 8(3), 351; https://doi.org/10.3390/microorganisms8030351 - 01 Mar 2020
Cited by 32 | Viewed by 4997
Abstract
Ralstonia solanacearum is an important soil-borne bacterial plant pathogen. In this study, an actinomycete strain named NEAU-HV9 that showed strong antibacterial activity against Ralstonia solanacearum was isolated from soil using an in vitro screening technique. Based on physiological and morphological characteristics and 98.90% [...] Read more.
Ralstonia solanacearum is an important soil-borne bacterial plant pathogen. In this study, an actinomycete strain named NEAU-HV9 that showed strong antibacterial activity against Ralstonia solanacearum was isolated from soil using an in vitro screening technique. Based on physiological and morphological characteristics and 98.90% of 16S rRNA gene sequence similarity with Streptomyces panaciradicis 1MR-8T, the strain was identified as a member of the genus Streptomyces. Tomato seedling and pot culture experiments showed that after pre-inoculation with the strain NEAU-HV9, the disease occurrence of tomato seedlings was effectively prevented for R. solanacearum. Then, a bioactivity-guided approach was employed to isolate and determine the chemical identity of bioactive constituents with antibacterial activity from strain NEAU-HV9. The structure of the antibacterial metabolite was determined as actinomycin D on the basis of extensive spectroscopic analysis. To our knowledge, this is the first report that actinomycin D has strong antibacterial activity against R. solanacearum with a MIC (minimum inhibitory concentration) of 0.6 mg L−1 (0.48 μmol L−1). The in vivo antibacterial activity experiment showed that actinomycin D possessed significant preventive efficacy against R. solanacearum in tomato seedlings. Thus, strain NEAU-HV9 could be used as BCA (biological control agent) against R. solanacearum, and actinomycin D might be a promising candidate for a new antibacterial agent against R. solanacearum. Full article
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15 pages, 7499 KiB  
Article
New Antimicrobial Phenyl Alkenoic Acids Isolated from an Oil Palm Rhizosphere-Associated Actinomycete, Streptomyces palmae CMU-AB204T
by Kanaporn Sujarit, Mihoko Mori, Kazuyuki Dobashi, Kazuro Shiomi, Wasu Pathom-aree and Saisamorn Lumyong
Microorganisms 2020, 8(3), 350; https://doi.org/10.3390/microorganisms8030350 - 01 Mar 2020
Cited by 13 | Viewed by 2924
Abstract
Basal stem rot (BSR), or Ganoderma rot disease, is the most serious disease associated with the oil palm plant of Southeast Asian countries. A basidiomycetous fungus, Ganoderma boninense, is the causative microbe of this disease. To control BSR in oil palm plantations, [...] Read more.
Basal stem rot (BSR), or Ganoderma rot disease, is the most serious disease associated with the oil palm plant of Southeast Asian countries. A basidiomycetous fungus, Ganoderma boninense, is the causative microbe of this disease. To control BSR in oil palm plantations, biological control agents are gaining attention as a major alternative to chemical fungicides. In the course of searching for effective actinomycetes as potential biological control agents for BSR, Streptomyces palmae CMU-AB204T was isolated from oil palm rhizosphere soil collected on the campus of Chiang Mai University. The culture broth of this strain showed significant antimicrobial activities against several bacteria and phytopathogenic fungi including G. boninense. Antifungal and antibacterial compounds were isolated by antimicrobial activity-guided purification using chromatographic methods. Their structures were elucidated by spectroscopic techniques, including Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS), Ultraviolet (UV), and Infrared (IR) analyses. The current study isolated new phenyl alkenoic acids 16 and three known compounds, anguinomycin A (7), leptomycin A (8), and actinopyrone A (9) as antimicrobial agents. Compounds 1 and 2 displayed broad antifungal activity, though they did not show antibacterial activity. Compounds 3 and 4 revealed a strong antibacterial activity against both Gram-positive and Gram-negative bacteria including the phytopathogenic strain Xanthomonas campestris pv. oryzae. Compounds 79 displayed antifungal activity against Ganoderma. Thus, the antifungal compounds obtained in this study may play a role in protecting oil palm plants from Ganoderma infection with the strain S. palmae CMU-AB204T. Full article
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11 pages, 835 KiB  
Article
Identification and Heterologous Expression of the Albucidin Gene Cluster from the Marine Strain Streptomyces Albus Subsp. Chlorinus NRRL B-24108
by Maksym Myronovskyi, Birgit Rosenkränzer, Marc Stierhof, Lutz Petzke, Tobias Seiser and Andriy Luzhetskyy
Microorganisms 2020, 8(2), 237; https://doi.org/10.3390/microorganisms8020237 - 10 Feb 2020
Cited by 16 | Viewed by 3059
Abstract
Herbicides with new modes of action and safer toxicological and environmental profiles are needed to manage the evolution of weeds that are resistant to commercial herbicides. The unparalleled structural diversity of natural products makes these compounds a promising source for new herbicides. In [...] Read more.
Herbicides with new modes of action and safer toxicological and environmental profiles are needed to manage the evolution of weeds that are resistant to commercial herbicides. The unparalleled structural diversity of natural products makes these compounds a promising source for new herbicides. In 2009, a novel nucleoside phytotoxin, albucidin, with broad activity against grass and broadleaf weeds was isolated from a strain of Streptomyces albus subsp. chlorinus NRRL B-24108. Here, we report the identification and heterologous expression of the previously uncharacterized albucidin gene cluster. Through a series of gene inactivation experiments, a minimal set of albucidin biosynthetic genes was determined. Based on gene annotation and sequence homology, a model for albucidin biosynthesis was suggested. The presented results enable the construction of producer strains for a sustainable supply of albucidin for biological activity studies. Full article
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13 pages, 2635 KiB  
Article
Diversity and Bioactive Potential of Actinobacteria from Unexplored Regions of Western Ghats, India
by Saket Siddharth, Ravishankar Rai Vittal, Joachim Wink and Michael Steinert
Microorganisms 2020, 8(2), 225; https://doi.org/10.3390/microorganisms8020225 - 07 Feb 2020
Cited by 23 | Viewed by 4696
Abstract
The search for novel bioactive metabolites continues to be of much importance around the world for pharmaceutical, agricultural, and industrial applications. Actinobacteria constitute one of the extremely interesting groups of microorganisms widely used as important biological contributors for a wide range of novel [...] Read more.
The search for novel bioactive metabolites continues to be of much importance around the world for pharmaceutical, agricultural, and industrial applications. Actinobacteria constitute one of the extremely interesting groups of microorganisms widely used as important biological contributors for a wide range of novel secondary metabolites. This study focused on the assessment of antimicrobial and antioxidant activity of crude extracts of actinobacterial strains. Western Ghats of India represents unique regions of biologically diverse areas called “hot spots”. A total of 32 isolates were obtained from soil samples of different forest locations of Bisle Ghat and Virjapet situated in Western Ghats of Karnataka, India. The isolates were identified as species of Streptomyces, Nocardiopsis, and Nocardioides by cultural, morphological, and molecular studies. Based on preliminary screening, seven isolates were chosen for metabolites extraction and to determine antimicrobial activity qualitatively (disc diffusion method) and quantitatively (micro dilution method) and scavenging activity against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. Crude extracts of all seven isolates exhibited fairly strong antibacterial activity towards MRSA strains (MRSA ATCC 33591, MRSA ATCC NR-46071, and MRSA ATCC 46171) with MIC varying from 15.62 to 125 μg/mL, whereas showed less inhibition potential towards Gram-negative bacteria Salmonella typhi (ATCC 25241) and Escherichia coli (ATCC 11775) with MIC of 125–500 μg/mL. The isolates namely S1A, SS5, SCA35, and SCA 11 inhibited Fusarium moniliforme (MTCC 6576) to a maximum extent with MIC ranging from 62.5 to 250 μg/mL. Crude extract of SCA 11 and SCA 13 exhibited potent scavenging activities against DPPH and ABTS radicals. The results from this study suggest that actinobacterial strains of Western Ghats are an excellent source of natural antimicrobial and antioxidant compounds. Further research investigations on purification, recovery, and structural characterization of the active compounds are to be carried out. Full article
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17 pages, 2212 KiB  
Article
Taxonomic Characterization, and Secondary Metabolite Analysis of Streptomyces triticiradicis sp. nov.: A Novel Actinomycete with Antifungal Activity
by Zhiyin Yu, Chuanyu Han, Bing Yu, Junwei Zhao, Yijun Yan, Shengxiong Huang, Chongxi Liu and Wensheng Xiang
Microorganisms 2020, 8(1), 77; https://doi.org/10.3390/microorganisms8010077 - 05 Jan 2020
Cited by 22 | Viewed by 5052
Abstract
The rhizosphere, an important battleground between beneficial microbes and pathogens, is usually considered to be a good source for isolation of antagonistic microorganisms. In this study, a novel actinobacteria with broad-spectrum antifungal activity, designated strain NEAU-H2T, was isolated from the rhizosphere [...] Read more.
The rhizosphere, an important battleground between beneficial microbes and pathogens, is usually considered to be a good source for isolation of antagonistic microorganisms. In this study, a novel actinobacteria with broad-spectrum antifungal activity, designated strain NEAU-H2T, was isolated from the rhizosphere soil of wheat (Triticum aestivum L.). 16S rRNA gene sequence similarity studies showed that strain NEAU-H2T belonged to the genus Streptomyces, with high sequence similarities to Streptomyces rhizosphaerihabitans NBRC 109807T (98.8%), Streptomyces populi A249T (98.6%), and Streptomyces siamensis NBRC 108799T (98.6%). Phylogenetic analysis based on 16S rRNA, atpD, gyrB, recA, rpoB, and trpB gene sequences showed that the strain formed a stable clade with S. populi A249T. Morphological and chemotaxonomic characteristics of the strain coincided with members of the genus Streptomyces. A combination of DNA–DNA hybridization results and phenotypic properties indicated that the strain could be distinguished from the abovementioned strains. Thus, strain NEAU-H2T belongs to a novel species in the genus Streptomyces, for which the name Streptomyces triticiradicis sp. nov. is proposed. In addition, the metabolites isolated from cultures of strain NEAU-H2T were characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. One new compound and three known congeners were isolated. Further, genome analysis revealed that the strain harbored diverse biosynthetic potential, and one cluster showing 63% similarity to natamycin biosynthetic gene cluster may contribute to the antifungal activity. The type strain is NEAU-H2T (= CCTCC AA 2018031T = DSM 109825T). Full article
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19 pages, 2771 KiB  
Article
Genome Mining Coupled with OSMAC-Based Cultivation Reveal Differential Production of Surugamide A by the Marine Sponge Isolate Streptomyces sp. SM17 When Compared to Its Terrestrial Relative S. albidoflavus J1074
by Eduardo L. Almeida, Navdeep Kaur, Laurence K. Jennings, Andrés Felipe Carrillo Rincón, Stephen A. Jackson, Olivier P. Thomas and Alan D.W. Dobson
Microorganisms 2019, 7(10), 394; https://doi.org/10.3390/microorganisms7100394 - 26 Sep 2019
Cited by 20 | Viewed by 4963
Abstract
Much recent interest has arisen in investigating Streptomyces isolates derived from the marine environment in the search for new bioactive compounds, particularly those found in association with marine invertebrates, such as sponges. Among these new compounds recently identified from marine Streptomyces isolates are [...] Read more.
Much recent interest has arisen in investigating Streptomyces isolates derived from the marine environment in the search for new bioactive compounds, particularly those found in association with marine invertebrates, such as sponges. Among these new compounds recently identified from marine Streptomyces isolates are the octapeptidic surugamides, which have been shown to possess anticancer and antifungal activities. By employing genome mining followed by an one strain many compounds (OSMAC)-based approach, we have identified the previously unreported capability of a marine sponge-derived isolate, namely Streptomyces sp. SM17, to produce surugamide A. Phylogenomics analyses provided novel insights on the distribution and conservation of the surugamides biosynthetic gene cluster (sur BGC) and suggested a closer relatedness between marine-derived sur BGCs than their terrestrially derived counterparts. Subsequent analysis showed differential production of surugamide A when comparing the closely related marine and terrestrial isolates, namely Streptomyces sp. SM17 and Streptomyces albidoflavus J1074. SM17 produced higher levels of surugamide A than S. albidoflavus J1074 under all conditions tested, and in particular producing >13-fold higher levels when grown in YD and 3-fold higher levels in SYP-NaCl medium. In addition, surugamide A production was repressed in TSB and YD medium, suggesting that carbon catabolite repression (CCR) may influence the production of surugamides in these strains. Full article
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17 pages, 4273 KiB  
Article
Characterization of Streptomyces sporangiiformans sp. nov., a Novel Soil Actinomycete with Antibacterial Activity against Ralstonia solanacearum
by Junwei Zhao, Liyuan Han, Mingying Yu, Peng Cao, Dongmei Li, Xiaowei Guo, Yongqiang Liu, Xiangjing Wang and Wensheng Xiang
Microorganisms 2019, 7(9), 360; https://doi.org/10.3390/microorganisms7090360 - 17 Sep 2019
Cited by 62 | Viewed by 5214
Abstract
Ralstonia solanacearum is a major phytopathogenic bacterium that attacks many crops and other plants around the world. In this study, a novel actinomycete, designated strain NEAU-SSA 1T, which exhibited antibacterial activity against Ralstonia solanacearum, was isolated from soil collected from [...] Read more.
Ralstonia solanacearum is a major phytopathogenic bacterium that attacks many crops and other plants around the world. In this study, a novel actinomycete, designated strain NEAU-SSA 1T, which exhibited antibacterial activity against Ralstonia solanacearum, was isolated from soil collected from Mount Song and characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics of the strain coincided with those of the genus Streptomyces. The 16S rRNA gene sequence analysis showed that the isolate was most closely related to Streptomyces aureoverticillatus JCM 4347T (97.9%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain formed a cluster with Streptomyces vastus JCM4524T (97.4%), S. cinereus DSM43033T (97.2%), S. xiangluensis NEAU-LA29T (97.1%) and S. flaveus JCM3035T (97.1%). The cell wall contained LL-diaminopimelic acid and the whole-cell hydrolysates were ribose, mannose and galactose. The polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), hydroxy-phosphatidylethanolamine (OH-PE), phosphatidylinositol (PI), two phosphatidylinositol mannosides (PIMs) and an unidentified phospholipid (PL). The menaquinones were MK-9(H4), MK-9(H6), and MK-9(H8). The major fatty acids were iso-C17:0, C16:0 and C17:1 ω9c. The DNA G+C content was 69.9 mol %. However, multilocus sequence analysis (MLSA) based on five other house-keeping genes (atpD, gyrB, recA, rpoB, and trpB), DNA–DNA relatedness, and physiological and biochemical data showed that the strain could be distinguished from its closest relatives. Therefore, it is proposed that strain NEAU-SSA 1T should be classified as representatives of a novel species of the genus Streptomyces, for which the name Streptomyces sporangiiformans sp. nov. is proposed. The type strain is NEAU-SSA 1T (=CCTCC AA 2017028T = DSM 105692T). Full article
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15 pages, 1296 KiB  
Article
Community Structures and Antifungal Activity of Root-Associated Endophytic Actinobacteria of Healthy and Diseased Soybean
by Chongxi Liu, Xiaoxin Zhuang, Zhiyin Yu, Zhiyan Wang, Yongjiang Wang, Xiaowei Guo, Wensheng Xiang and Shengxiong Huang
Microorganisms 2019, 7(8), 243; https://doi.org/10.3390/microorganisms7080243 - 07 Aug 2019
Cited by 33 | Viewed by 3712
Abstract
The present study was conducted to examine the influence of a pathogen Sclerotinia sclerotiorum (Lib.) de Bary on the actinobacterial community associated with the soybean roots. A total of 70 endophytic actinobacteria were isolated from the surface-sterilized roots of either healthy or diseased [...] Read more.
The present study was conducted to examine the influence of a pathogen Sclerotinia sclerotiorum (Lib.) de Bary on the actinobacterial community associated with the soybean roots. A total of 70 endophytic actinobacteria were isolated from the surface-sterilized roots of either healthy or diseased soybeans, and they were distributed under 14 genera. Some rare genera, including Rhodococcus, Kribbella, Glycomyces, Saccharothrix, Streptosporangium and Cellulosimicrobium, were endemic to the diseased samples, and the actinobacterial community was more diverse in the diseased samples compared with that in the heathy samples. Culture-independent analysis of root-associated actinobacterial community using the high-throughput sequencing approach also showed similar results. Four Streptomyces strains that were significantly abundant in the diseased samples exhibited strong antagonistic activity with the inhibition percentage of 54.1–87.6%. A bioactivity-guided approach was then employed to isolate and determine the chemical identity of antifungal constituents derived from the four strains. One new maremycin analogue, together with eight known compounds, were detected. All compounds showed significantly antifungal activity against S. sclerotiorum with the 50% inhibition (EC50) values of 49.14–0.21 mg/L. The higher actinobacterial diversity and more antifungal strains associated with roots of diseased plants indicate a possible role of the root-associated actinobacteria in natural defense against phytopathogens. Furthermore, these results also suggest that the root of diseased plant may be a potential reservoir of actinobacteria producing new agroactive compounds. Full article
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10 pages, 2758 KiB  
Communication
Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria Reveals Unexplored Biosynthetic Potential
by Katherine Gregory, Laura A. Salvador, Shukria Akbar, Barbara I. Adaikpoh and D. Cole Stevens
Microorganisms 2019, 7(6), 181; https://doi.org/10.3390/microorganisms7060181 - 24 Jun 2019
Cited by 26 | Viewed by 5753
Abstract
Coinciding with the increase in sequenced bacteria, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a critical component of natural product discovery. The order Myxococcales, a reputable source of biologically active secondary metabolites, spans three suborders which all include natural [...] Read more.
Coinciding with the increase in sequenced bacteria, mining of bacterial genomes for biosynthetic gene clusters (BGCs) has become a critical component of natural product discovery. The order Myxococcales, a reputable source of biologically active secondary metabolites, spans three suborders which all include natural product producing representatives. Utilizing the BiG-SCAPE-CORASON platform to generate a sequence similarity network that contains 994 BGCs from 36 sequenced myxobacteria deposited in the antiSMASH database, a total of 843 BGCs with lower than 75% similarity scores to characterized clusters within the MIBiG database are presented. This survey provides the biosynthetic diversity of these BGCs and an assessment of the predicted chemical space yet to be discovered. Considering the mere snapshot of myxobacteria included in this analysis, these untapped BGCs exemplify the potential for natural product discovery from myxobacteria. Full article
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13 pages, 11501 KiB  
Article
Evaluation of Antimicrobial, Enzyme Inhibitory, Antioxidant and Cytotoxic Activities of Partially Purified Volatile Metabolites of Marine Streptomyces sp.S2A
by Saket Siddharth and Ravishankar Rai Vittal
Microorganisms 2018, 6(3), 72; https://doi.org/10.3390/microorganisms6030072 - 18 Jul 2018
Cited by 43 | Viewed by 6509
Abstract
In the present study, marine actinobacteria Streptomyces sp.S2A was isolated from the Gulf of Mannar, India. Identification was carried out by 16S rRNA analysis. Bioactive metabolites were extracted by solvent extraction method. The metabolites were assayed for antagonistic activity against bacterial and fungal [...] Read more.
In the present study, marine actinobacteria Streptomyces sp.S2A was isolated from the Gulf of Mannar, India. Identification was carried out by 16S rRNA analysis. Bioactive metabolites were extracted by solvent extraction method. The metabolites were assayed for antagonistic activity against bacterial and fungal pathogens, inhibition of α-glucosidase and α-amylase enzymes, antioxidant activity and cytotoxic activity against various cell lines. The actinobacterial extract showed significant antagonistic activity against four gram-positive and two gram-negative pathogens. Excellent reduction in the growth of fungal pathogens was also observed. The minimum inhibitory concentration of the partially purified extract (PPE) was determined as 31.25 μg/mL against Klebsiella pneumoniae, 15.62 μg/mL against Staphylococcus epidermidis, Staphylococcus aureus and Bacillus cereus. The lowest MIC was observed against Micrococcus luteus as 7.8 μg/mL. MIC against fungal pathogens was determined as 62.5 μg/mL against Bipolaris maydis and 15.62 μg/mL against Fusarium moniliforme. The α-glucosidase and α-amylase inhibitory potential of the fractions were carried out by microtiter plate method. IC50 value of active fraction for α-glucosidase and α-amylase inhibition was found to be 21.17 μg/mL and 20.46 μg/mL respectively. The antioxidant activity of partially purified extract (PPE) (DPPH, ABTS, FRAP and Metal chelating activity) were observed and were also found to have significant cytotoxic activity against HT-29, MDA and U-87MG cell lines. The compound analysis was performed using gas chromatography-mass spectrometry (GC-MS) and resulted in three constituents; pyrrolo[1–a]pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl)-, being the main component (80%). Overall, the strain possesses a wide spectrum of antimicrobial, enzyme inhibitory, antioxidant and cytotoxic activities which affords the production of significant bioactive metabolites as potential pharmacological agents. Full article
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Review

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18 pages, 4877 KiB  
Review
Biosynthesis of Polyketides in Streptomyces
by Chandra Risdian, Tjandrawati Mozef and Joachim Wink
Microorganisms 2019, 7(5), 124; https://doi.org/10.3390/microorganisms7050124 - 06 May 2019
Cited by 71 | Viewed by 11547
Abstract
Polyketides are a 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, [...] Read more.
Polyketides are a 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 the 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 responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs. Full article
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23 pages, 6303 KiB  
Review
Diversity of Myxobacteria—We Only See the Tip of the Iceberg
by Kathrin I. Mohr
Microorganisms 2018, 6(3), 84; https://doi.org/10.3390/microorganisms6030084 - 11 Aug 2018
Cited by 66 | Viewed by 11059
Abstract
The discovery of new antibiotics is mandatory with regard to the increasing number of resistant pathogens. One approach is the search for new antibiotic producers in nature. Among actinomycetes, Bacillus species, and fungi, myxobacteria have been a rich source for bioactive secondary metabolites [...] Read more.
The discovery of new antibiotics is mandatory with regard to the increasing number of resistant pathogens. One approach is the search for new antibiotic producers in nature. Among actinomycetes, Bacillus species, and fungi, myxobacteria have been a rich source for bioactive secondary metabolites for decades. To date, about 600 substances could be described, many of them with antibacterial, antifungal, or cytostatic activity. But, recent cultivation-independent studies on marine, terrestrial, or uncommon habitats unequivocally demonstrate that the number of uncultured myxobacteria is much higher than would be expected from the number of cultivated strains. Although several highly promising myxobacterial taxa have been identified recently, this so-called Great Plate Count Anomaly must be overcome to get broader access to new secondary metabolite producers. In the last years it turned out that especially new species, genera, and families of myxobacteria are promising sources for new bioactive metabolites. Therefore, the cultivation of the hitherto uncultivable ones is our biggest challenge. Full article
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15 pages, 1652 KiB  
Review
Antiviral Compounds from Myxobacteria
by Lucky S. Mulwa and Marc Stadler
Microorganisms 2018, 6(3), 73; https://doi.org/10.3390/microorganisms6030073 - 19 Jul 2018
Cited by 21 | Viewed by 6869
Abstract
Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent [...] Read more.
Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy. Viral-based illnesses are further aggravated by co-infections, such as an HIV patient co-infected with HBV or HCV. The drugs used to treat or manage HIV tend to increase the pathogenesis of HBV and HCV. Hence, novel antiviral drug candidates should ideally have broad-spectrum activity and no negative drug-drug interactions. Myxobacteria are in the focus of this review since they produce numerous structurally and functionally unique bioactive compounds, which have only recently been screened for antiviral effects. This research has already led to some interesting findings, including the discovery of several candidate compounds with broad-spectrum antiviral activity. The present review looks at myxobacteria-derived antiviral secondary metabolites. Full article
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10 pages, 1344 KiB  
Review
Chemical Elicitors of Antibiotic Biosynthesis in Actinomycetes
by Anton P. Tyurin, Vera A. Alferova and Vladimir A. Korshun
Microorganisms 2018, 6(2), 52; https://doi.org/10.3390/microorganisms6020052 - 08 Jun 2018
Cited by 19 | Viewed by 6199
Abstract
Whole genome sequencing of actinomycetes has uncovered a new immense realm of microbial chemistry and biology. Most biosynthetic gene clusters present in genomes were found to remain “silent” under standard cultivation conditions. Some small molecules—chemical elicitors—can be used to induce the biosynthesis of [...] Read more.
Whole genome sequencing of actinomycetes has uncovered a new immense realm of microbial chemistry and biology. Most biosynthetic gene clusters present in genomes were found to remain “silent” under standard cultivation conditions. Some small molecules—chemical elicitors—can be used to induce the biosynthesis of antibiotics in actinobacteria and to expand the chemical diversity of secondary metabolites. Here, we outline a brief account of the basic principles of the search for regulators of this type and their application. Full article
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