A new dithiolopyrrolone antibiotic triggered by a long fermentation of Saccharothrix algeriensis NRRL B-24137 in sorbic acid-amended medium.

Saccharothrix algeriensis NRRL B-24137 is an actinobacterium isolated from Algerian Saharan soil. It produces bioactive compounds belonging to the dithiolopyrrolone class of antibiotics, which are characterized by the possession of a unique pyrrolinonodithiole nucleus. Dithiolopyrrolones are known for their strong antibacterial and antifungal activities. This class of antibiotics generated great interest after the discovery of their anticancer properties. In this study, an antibiotic named PR11, produced after a long bacterial fermentation (11 days) in sorbic acid-containing culture broth, was characterized as a new dithiolopyrrolone derivative. After HPLC analysis and purification, the chemical structure of this antibiotic was determined by 1 H- and 13 C-nuclear magnetic resonance, mass and UV-visible data. PR11 was thus characterized as an iso-hexanoyl-pyrrothine, a novel dithiolopyrrolone derivative. The minimum inhibitory concentrations of the new induced antibiotic were determined against several pathogenic micro-organisms. A moderate to strong activity was noted against all Gram-positive bacteria, filamentous fungi and yeasts tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Given the strong activities of dithiolopyrrolones against diverse prokaryotic and eukaryotic micro-organisms including potent selective-anticancer activity, the discovery of new-related derivatives draw continuous attention for therapeutic research. Depending on nature and concentration of added precursor, Saccharothrix algeriensis NRRL B-24137 produce several dithiolopyrrolone coumpounds. In this study, sorbic acid addition combined to long fermentation duration was shown to induce the biosynthesis of a novel dithiolopyrrolone derivative. After purification and full spectroscopic and spectrometric study, the compound was characterized as iso-hexanoyl-pyrrothine. In the future investigation for novel dithiolopyrrolone discovery, fermentation duration should be regarded as a key parameter as well.

Effective biosynthesis of benzoyl-pyrrothine dithiolopyrrolone antibiotic by cinnamic acid-precursor addition in culture of Saccharothrix algeriensis NRRL B-24137.

Dithiolopyrrolone antibiotics, produced by several micro-organisms, are known for their strong antimicrobial and antitumor activities. Among of this micro-organisms, Saccharothrix algeriensis NRRL B-24137, a rare actinobacterium, has the ability to produce several dithiolopyrrolones derivatives depending on precursors added in the culture medium. After 10 days of strain fermentation on semi-synthetic medium supplemented with cinnamic acid and HPLC purification, biosynthesis of benzoyl-pyrrothine dithiolopyrrolone was evidenced through complete spectroscopic (UV-visible and 1H and 13C NMR) and spectrometric (electron impact mass spectrum) analyses. The pure molecule showed appreciable minimum inhibitory concentration values against several Gram-positive bacteria and filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Dithiolopyrrolone antibiotics, known for their strong antimicrobial activities, gained greater interest after the discovery of their antitumor properties. Depending on precursors added, Saccharothrix algeriensis NRRL B-24137 has the ability to produce several dithiolopyrrolones derivatives. Since biological activities of dithiolopyrrolones are related to their variable structure, discover of new natural analogues to be therapeutically explored remains a significant framework of research. In this study, a new dithiolopyrrolone derivative was purified from the fermentation broth of S. algeriensis NRRL B-24137. This new antibiotic, characterized as benzoyl-pyrrothine dithiolopyrrolone, was induced by adding cinnamic acid, as precursor, to a semi-synthetic medium.

A novel hydroxamic acid-containing antibiotic produced by a Saharan soil-living Streptomyces strain.

During screening for potentially antimicrobial actinobacteria, a highly antagonistic strain, designated WAB9, was isolated from a Saharan soil of Algeria. A polyphasic approach characterized the strain taxonomically as a member of the genus Streptomyces. The strain WAB9 exhibited a broad spectrum of antimicrobial activity toward various multidrug-resistant micro-organisms. A PCR-based assay of genomic potential for producing bioactive metabolites revealed the presence of PKS-II gene. After 6 days of strain fermentation, one bioactive compound was extracted from the remaining aqueous phase and then purified by HPLC. The chemical structure of the compound was determined by spectroscopic (UV-visible, and (1)H and (13)C NMR) and spectrometric analysis. The compound was identified to be 2-amino-N-(2-amino-3-phenylpropanoyl)-N-hydroxy-3-phenylpropanamide, a novel hydroxamic acid-containing molecule. The pure molecule showed appreciable minimum inhibitory concentration values against a selection of drug-resistant bacteria, filamentous fungi and yeasts. Significance and impact of the study: This study presents the isolation of a Streptomyces strain, named WAB9, from a Saharan soil in Algeria. This strain was found to produce a new hydroxamic acid-containing molecule with interesting antimicrobial activities towards various multidrug-resistant micro-organisms. Although hydroxamic acid-containing molecules are known to exhibit low toxicities in general, only real evaluations of the toxicity levels could decide on the applications for which this new molecule is potentially most appropriate. Thus, this article provides a new framework of research.

Characterization and antagonistic properties of Streptomyces strains isolated from Saharan soils, and evaluation of their ability to control seedling blight of barley caused by Fusarium culmorum.

UNLABELLED: During a screening for potential plant disease control actinomycetes, a total of 133 strains were isolated from Saharan soil samples of seven Algerian regions by dilution technique on chitin-vitamins agar medium. Screening for antagonistic properties using streak assay method showed that 25% of isolates demonstrated strong activities against a wide range of plant pathogenic fungi. Due to their strong anti-Fusarium activities, six of these isolates were selected and subsequently related to Streptomyces species by polyphasic analysis. These isolates were evaluated for their biocontrol ability against Fusarium culmorum, a serious pathogenic fungus of cereals crops related to damping-off and seedling blight resulting in yield loss. Barley seeds were chosen as cereal plant model. Surface bacterized seeds with TW3, RI3 and TW2 strains expressed the highest performances and permit to reduce significantly both the disease occurrence on seedlings (62-76%) and the extent of seedling blight symptoms (over than 95%). However, a negative effect on plant establishment was observed for RI3 treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: The genus Fusarium is considered to be one of the most problematic phytopathogenic fungi for crop culture worldwide. Inside this genus, F. culmorum is the aetiological agent of seedling blight in various monocotyledonous plants such as barley and cause extensive yield and quality losses in humid and semi-humid regions. Biological control may be a successful alternative to chemical control, particularly with the controversy surrounding the use of the fungicides and the limited obtained results to control F. culmorum. This study highlights the effectiveness of some antagonistic Streptomyces isolated from Algerian Saharan soils to control F. culmorum by the reduction in disease occurrence and disease severity suggesting their use on microbial biocontrol formulation against soilborne diseases.