Streptomyces, Greek Habitats and Novel Pharmaceuticals: A Promising Challenge

Bacteria of the genus Streptomyces produce a very large number of secondary metabolites, many of which are of vital importance to modern medicine. There is great interest in the discovery of novel pharmaceutical compounds derived from strepomycetes, since novel antibiotics, anticancer and compounds for treating other conditions are urgently needed. Greece, as proven by recent research, possesses microbial reservoirs with a high diversity of Streptomyces populations, which provide a rich pool of strains with potential pharmaceutical value. This review examines the compounds of pharmaceutical interest that have been derived from Greek Streptomyces isolates. The compounds reported in the literature include antibiotics, antitumor compounds, biofilm inhibitors, antiparasitics, bacterial toxin production inhibitors and antioxidants. The streptomycete biodiversity of Greek environments remains relatively unexamined and is therefore a very promising resource for potential novel pharmaceuticals.

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Genome-wide screening antifungal genes in Streptomyces griseus S4-7, a Fusarium wilt disease suppressive microbial agent

FEMS Microbiology Letters ◽

10.1093/femsle/fnz133 ◽

2019 ◽

Vol 366 (12) ◽

Cited By ~ 1

Author(s):

Sung Won Hong ◽

Da-Ran Kim ◽

Youn Sang Kwon ◽

Youn-Sig Kwak

Keyword(s):

Antifungal Activity ◽

Secondary Metabolites ◽

Fusarium Wilt ◽

Streptomyces Griseus ◽

Wilt Disease ◽

Inverse Pcr ◽

Genus Streptomyces ◽

Fusarium Wilt Disease ◽

Genome Wide ◽

A Genome

ABSTRACT Streptomyces is a widely studied bacterial genus, particularly with regard to secondary metabolites and antibiotics production. Streptomyces griseus S4–7 was isolated from a strawberry Fusarium wilt disease suppressive soil, and its biological control ability has been well established. However, the antifungal mechanism of strain S4–7 is not yet fully understood at the molecular and biochemical level. Therefore, in this study we created a random mutant library for strain S4–7 with the Tn5 transposon element to investigate antifungal traits on a genome-wide scale. In total 4646 individual mutant strains were created and 13 mutants were selected based on loss of antifungal activity. The knockout genes were identified as electron transfer oxidoreductase (eto),sigma factor-70(sig70) and nrps by Inverse PCR (I-PCR). eto regulates the geranylgeranyl reductase gene, which is involved in terpenoid-quinone biosynthesis, an important factor in cell fitness. In the △eto strain, expression of wbl, a master regulator of the production of secondary metabolites, was significantly reduced. sig70 is responsible for the cell differentiation sensing mechanism in genus Streptomyces. △nrps showed decreased production of hybrid peptide-polyketide siderophores. These results suggest that S. griseus S4–7 may have various antifungal mechanisms, and each mechanism is essential to maximal antifungal activity.

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Dermatologic Manifestations of Infectious Disease

10.1093/med/9780199976805.003.0044 ◽

2016 ◽

Author(s):

Lisa Cuttle

Keyword(s):

Toxic Shock Syndrome ◽

Vibrio Vulnificus ◽

Spotted Fever ◽

Rocky Mountain ◽

Toxin Production ◽

Skin Lesions ◽

Bacterial Toxin ◽

Streptococcal Toxic Shock Syndrome ◽

Rocky Mountain Spotted Fever ◽

Toxic Shock

Toxic infectious exfoliative conditions include staphylococcal toxic shock syndrome (TSS), streptococcal toxic shock syndrome (STSS), and staphylococcal scalded skin syndrome (SSSS). All three are mediated by bacterial toxin production and are considerations in the differential diagnosis of a febrile, hypotensive patient with a rash. Meningococcemia is potentially fatal and extremely contagious with a short incubation period. Disseminated gonococcal infection (DGI) presents with tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis or with purulent arthritis but without skin lesions. Ecthyma gangrenosum (EG) is a cutaneous manifestation of Pseudomonas aeruginosa infection. Rocky Mountain Spotted Fever (RMSF) is caused by Rickettsia rickettsii, most commonly transmitted by the American dog tick. Patients present with nonspecific symptoms, such as fever, headache, myalgias, arthralgias, nausea, vomiting, and abdominal pain. Finally, vibrio vulnificus is a gram-negative bacterium that causes serious wound infections, sepsis, and diarrhea in patients exposed to shellfish or marine water.

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The Phylum Bryozoa as a Promising Source of Anticancer Drugs

Marine Drugs ◽

10.3390/md17080477 ◽

2019 ◽

Vol 17 (8) ◽

pp. 477 ◽

Cited By ~ 6

Author(s):

Figuerola ◽

Avila

Keyword(s):

Secondary Metabolites ◽

Anticancer Agents ◽

Biological Activities ◽

Chemical Diversity ◽

Anticancer Properties ◽

Antitumor Compounds ◽

Wide Range ◽

Drug Synthesis ◽

Low Toxicity ◽

Promising Source

Recent advances in sampling and novel techniques in drug synthesis and isolation have promoted the discovery of anticancer agents from marine organisms to combat this major threat to public health worldwide. Bryozoans, which are filter-feeding, aquatic invertebrates often characterized by a calcified skeleton, are an excellent source of pharmacologically interesting compounds including well-known chemical classes such as alkaloids and polyketides. This review covers the literature for secondary metabolites isolated from marine cheilostome and ctenostome bryozoans that have shown potential as cancer drugs. Moreover, we highlight examples such as bryostatins, the most known class of marine-derived compounds from this animal phylum, which are advancing through anticancer clinical trials due to their low toxicity and antineoplastic activity. The bryozoan antitumor compounds discovered until now show a wide range of chemical diversity and biological activities. Therefore, more research focusing on the isolation of secondary metabolites with potential anticancer properties from bryozoans and other overlooked taxa covering wider geographic areas is needed for an efficient bioprospecting of natural products.

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In-Vitro Screening and Biosynthesis of Secondary Metabolites from a New Streptomyces sp. SA1 from a Marine Environment

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200622120850 ◽

2020 ◽

Vol 21 (13) ◽

pp. 1333-1341

Author(s):

Mohammed A. Almalki

Keyword(s):

Secondary Metabolites ◽

Marine Environment ◽

Traditional Method ◽

Culture Medium ◽

Antimicrobial Agents ◽

Resistant Bacteria ◽

Genus Streptomyces ◽

Streptomyces Sp ◽

Medium Components ◽

Beef Extract

Background: Streptomyces sp. produces various antibiotic agents and the number of lead molecules from the genus Streptomyces increased rapidly in recent years. Drug resistance against various commercially available antibiotics is one of the important problems throughout the world. Streptomyces spp. produce various antimicrobials with potent activity against drug-resistant bacteria. Methods: Streptomyces sp. SA1 was isolated from the marine environment for the biosynthesis of antibiotics. The important variables influencing secondary metabolite biosynthesis were optimized to increase the biosynthesis of antimicrobial agents using the traditional method and statistical approach. Results: Streptomyces sp. SA1 produced novel antibiotics and the process variables were optimized by the traditional method (One-variable-at-a-time approach). Maltose showed maximum antimicrobial activity (220 U/mL). Analysis of the nitrogen, the effect of nitrogen sources revealed that beef extract incorporated culture medium showed rich antibacterial activity (188/mL). Among the ionic sources, KCl significantly influenced antibiotic production. Maltose, beef extract and KCl were considered as the most influencing medium components. Antimicrobial agent biosynthesis was achieved with maltose 1.22 g/L, beef extract 0.93 g/L and KCl 0.27 g/L in response surface methodology. Conclusion: Actinomycetes, especially Streptomyces, play an important role as a source for bioactive compounds that are used to treat infections, and many other diseases. The isolated Streptomyces sp. was a good producer of antibacterial agent, which required various nutritional supplements in the culture medium. The optimized medium components investigated in this study will be useful for future studies with the mass production of secondary metabolites.

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Characterization of the Immune Response in Patients Infected with Clostridioides Difficile Due to Serum Biomarkers' Level with Correlation to Clinical Characteristics and Bacterial Toxin Production

10.21203/rs.3.rs-35006/v1 ◽

2020 ◽

Author(s):

Dor Gotshal ◽

Maya Azrad ◽

Zohar Hamo ◽

Orna Nitzan ◽

Avi Peretz

Keyword(s):

Clinical Characteristics ◽

Severe Disease ◽

Toxin Production ◽

Bacterial Toxin ◽

Serum Samples ◽

Clostridioides Difficile ◽

Cytokines And Chemokines ◽

Immunological Markers ◽

Laboratory Confirmation ◽

Moderate Disease

Abstract Background: Clostridioides difficile infection (CDI) have a high risk for complications up to death which requires identifying patients with severe disease and treating them accordingly. We examined the serum level of 6 cytokines and chemokines (IL-6, IL-21, IL-23, IL-33, BCA-1, TRAIL) and we checked the correlation between them to the patients' clinical characteristics and the bacterial strain.Methods: Concentrations of 6 cytokines and chemokines were measured using the MILLIPLEX®MAP kit (Billerica, USA) based on the Luminex xMAP® technology, in serum samples, attained from 54 CDI patients within a median time of 24-48 hours after laboratory confirmation of C. difficile presence. The demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined according to the guidelines of the "Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America" (SHEA-IDSA).Results: Out of 54 patients (mean age, 76.6 years, 61.1% female), 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. Two immunological markers were associated with a more severe disease: IL-16 (p = 0.005) and BCA-1 (p = 0.012). The study didn’t show a correlation between the immunological markers to the gender, the type of toxin which produced by the bacteria, in hospital mortality and infection acquisition.Conclusions: cytokines and chemokines may serve as a biomarker for early prediction of CDI severity in the future. Improved and more accessible assessment of CDI severity will contribute to adjustment of the medical treatment which will lead to a better patient outcome and hopefully will reduce the patient's mortality.

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Bacterial Toxin-Antitoxin Systems as Targets for the Development of Novel Antibiotics

Enzyme-Mediated Resistance to Antibiotics ◽

10.1128/9781555815615.ch19 ◽

2014 ◽

pp. 313-329 ◽

Cited By ~ 9

Author(s):

Juan C. Alonso ◽

Dolors Balsa ◽

Izhack Cherny ◽

Susanne K. Christensen ◽

Manuel Espinosa ◽

...

Keyword(s):

Bacterial Toxin ◽

Novel Antibiotics

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Integrated omics unveil the secondary metabolic landscape of a basal dinoflagellate

BMC Biology ◽

10.1186/s12915-020-00873-6 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Girish Beedessee ◽

Takaaki Kubota ◽

Asuka Arimoto ◽

Koki Nishitsuji ◽

Ross F. Waller ◽

...

Keyword(s):

Secondary Metabolites ◽

Harmful Algal Blooms ◽

Algal Blooms ◽

Toxin Production ◽

Mrna Isoforms ◽

Peptide Synthetase ◽

Integrated Omics ◽

Large Genome Size ◽

Post Transcriptional Regulation ◽

First Time

Abstract Background Some dinoflagellates cause harmful algal blooms, releasing toxic secondary metabolites, to the detriment of marine ecosystems and human health. Our understanding of dinoflagellate toxin biosynthesis has been hampered by their unusually large genomes. To overcome this challenge, for the first time, we sequenced the genome, microRNAs, and mRNA isoforms of a basal dinoflagellate, Amphidinium gibbosum, and employed an integrated omics approach to understand its secondary metabolite biosynthesis. Results We assembled the ~ 6.4-Gb A. gibbosum genome, and by probing decoded dinoflagellate genomes and transcriptomes, we identified the non-ribosomal peptide synthetase adenylation domain as essential for generation of specialized metabolites. Upon starving the cells of phosphate and nitrogen, we observed pronounced shifts in metabolite biosynthesis, suggestive of post-transcriptional regulation by microRNAs. Using Iso-Seq and RNA-seq data, we found that alternative splicing and polycistronic expression generate different transcripts for secondary metabolism. Conclusions Our genomic findings suggest intricate integration of various metabolic enzymes that function iteratively to synthesize metabolites, providing mechanistic insights into how dinoflagellates synthesize secondary metabolites, depending upon nutrient availability. This study provides insights into toxin production associated with dinoflagellate blooms. The genome of this basal dinoflagellate provides important clues about dinoflagellate evolution and overcomes the large genome size, which has been a challenge previously.

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A Comprehensive Review on Medicinal Plants as Antimicrobial Therapeutics: Potential Avenues of Biocompatible Drug Discovery

Metabolites ◽

10.3390/metabo9110258 ◽

2019 ◽

Vol 9 (11) ◽

pp. 258 ◽

Cited By ~ 31

Author(s):

Uttpal Anand ◽

Nadia Jacobo-Herrera ◽

Ammar Altemimi ◽

Naoufal Lakhssassi

Keyword(s):

Multidrug Resistance ◽

Drug Discovery ◽

Antimicrobial Resistance ◽

Medicinal Plants ◽

Secondary Metabolites ◽

Comprehensive Review ◽

Rich Diversity ◽

Potential Benefits ◽

Wonder Drug ◽

Novel Antibiotics

The war on multidrug resistance (MDR) has resulted in the greatest loss to the world’s economy. Antibiotics, the bedrock, and wonder drug of the 20th century have played a central role in treating infectious diseases. However, the inappropriate, irregular, and irrational uses of antibiotics have resulted in the emergence of antimicrobial resistance. This has resulted in an increased interest in medicinal plants since 30–50% of current pharmaceuticals and nutraceuticals are plant-derived. The question we address in this review is whether plants, which produce a rich diversity of secondary metabolites, may provide novel antibiotics to tackle MDR microbes and novel chemosensitizers to reclaim currently used antibiotics that have been rendered ineffective by the MDR microbes. Plants synthesize secondary metabolites and phytochemicals and have great potential to act as therapeutics. The main focus of this mini-review is to highlight the potential benefits of plant derived multiple compounds and the importance of phytochemicals for the development of biocompatible therapeutics. In addition, this review focuses on the diverse effects and efficacy of herbal compounds in controlling the development of MDR in microbes and hopes to inspire research into unexplored plants with a view to identify novel antibiotics for global health benefits.

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Biologically active secondary metabolites from Actinomycetes

Open Life Sciences ◽

10.2478/s11535-012-0036-1 ◽

2012 ◽

Vol 7 (3) ◽

pp. 373-390 ◽

Cited By ~ 34

Author(s):

Jolanta Solecka ◽

Joanna Zajko ◽

Magdalena Postek ◽

Aleksandra Rajnisz

Keyword(s):

Biological Activity ◽

Secondary Metabolites ◽

Chemical Structure ◽

Multidrug Resistant ◽

Biologically Active ◽

Plant Roots ◽

Bacterial Strains ◽

Genus Streptomyces ◽

Gram Negative ◽

Potential Source

AbstractSecondary metabolites obtained from Actinomycetales provide a potential source of many novel compounds with antibacterial, antitumour, antifungal, antiviral, antiparasitic and other properties. The majority of these compounds are widely used as medicines for combating multidrug-resistant Gram-positive and Gram-negative bacterial strains. Members of the genus Streptomyces are profile producers of previously-known secondary metabolites. Actinomycetes have been isolated from terrestrial soils, from the rhizospheres of plant roots, and recently from marine sediments. This review demonstrates the diversity of secondary metabolites produced by actinomycete strains with respect to their chemical structure, biological activity and origin. On the basis of this diversity, this review concludes that the discovery of new bioactive compounds will continue to pose a great challenge for scientists.

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An Overview of the Chemical Characteristics, Bioactivity and Achievements Regarding the Therapeutic Usage of Acetogenins from Annona cherimola Mill

Molecules ◽

10.3390/molecules26102926 ◽

2021 ◽

Vol 26 (10) ◽

pp. 2926

Author(s):

Alexandra G. Durán ◽

M. Teresa Gutiérrez ◽

Francisco J. R. Mejías ◽

José M. G. Molinillo ◽

Francisco A. Macías

Keyword(s):

Secondary Metabolites ◽

Traditional Medicine ◽

Chemical Diversity ◽

Chemical Characteristics ◽

Annonaceous Acetogenins ◽

Annona Cherimola ◽

Antitumor Compounds ◽

Custard Apple ◽

Synthetic Derivatives ◽

Derivatives Of

Annona cherimola Mill., or the custard apple, is one of the species belonging to the Annonaceae family, is widely used in traditional medicine, and has been reported to be a valuable source of bioactive compounds. A unique class of secondary metabolites derived from this family are Annonaceous acetogenins, lipophilic polyketides considered to be amongst the most potent antitumor compounds. This review provides an overview of the chemical diversity, isolation procedures, bioactivity, modes of application and synthetic derivatives of acetogenins from A. cherimola Mill.

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