Bioprospecting the potential of metabolites from a Saharan saline soil strain Nocardiopsis dassonvillei GSBS4.

Saharan soil samples collected in El-Oued province have been investigated for actinobacteria as a valuable source for the production of bioactive metabolites. A total of 273 isolates were obtained and subjected to antagonistic activity tests against human pathogenic germs. A strain with a broad-spectrum antimicrobial activity was selected and identified as Nocardiopsis dassonvillei GSBS4, with high sequence similarities to N. dassonvillei subsp. dassonvilleiT X97886.1 (99%) based on polyphasic taxonomy approach and 16S ribosomal ribonucleic acid gene sequence analysis. The GSBS4 ethyl acetate crude extract showed strong antibacterial activity towards pathogenic bacteria and Candida albicans. It inhibited biofilm formation by Staphylococcus aureus and methicillin-resistant S. aureus with minimum inhibitory concentrations estimated at 0.144 and 1.15 mg·mL-1 , respectively. A 44% biofilm reduction was obtained for S. aureus and 61% for Pseudomonas aeruginosa. Furthermore, phenols composition of the crude extract showed a significant dose-dependent antioxidant activity by α-diphenyl-ß-picrylhydrazyl (57.21%) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (64.29%) radicals scavenging assays. Although no inhibition was obtained on human coronavirus human coronavirus (HCoV) 229E and on model enterovirus (poliovirus 1) infection, a dose-dependent increase in cell viability of HCoV 229E-infected cells was noticed as the viability increased from 21% to 37%. Bioassay-guided fractionation of the crude extract gave a fraction showing antibacterial activity, which was analyzed by liquid chromatography-electrospray mass spectrometric technique, providing structural features on a major purple metabolite.

Actinobacteria Derived from Algerian Ecosystems as a Prominent Source of Antimicrobial Molecules.

Actinobacteria, in particular "rare actinobacteria" isolated from extreme ecosystems, remain the most inexhaustible source of novel antimicrobials, offering a chance to discover new bioactive metabolites. This is the first overview on actinobacteria isolated in Algeria since 2002 to date with the aim to present their potential in producing bioactive secondary metabolites. Twenty-nine new species and one novel genus have been isolated, mainly from the Saharan soil and palm groves, where 37.93% of the most abundant genera belong to Saccharothrix and Actinopolyspora. Several of these strains were found to produce antibiotics and antifungal metabolites, including 17 new molecules among the 50 structures reported, and some of these antibacterial metabolites have shown interesting antitumor activities. A series of approaches used to enhance the production of bioactive compounds is also presented as the manipulation of culture media by both classical methods and modeling designs through statistical strategies and the associations with diverse organisms and strains. Focusing on the Algerian natural sources of antimicrobial metabolites, this work is a representative example of the potential of a closely combined study on biology and chemistry of natural products.

Modeling improved production of the chemotherapeutic polypeptide actinomycin D by a novel Streptomyces sp. strain from a Saharan soil.

The novel bioactive actinobacterial strain GSBNT10 obtained from a Saharan soil, was taxonomically characterized using a polyphasic approach. 16S rRNA gene sequence analysis supported the classification of the isolate within the genus Streptomyces indicating it as a novel species. The major metabolite responsible of the bioactivity was purified and structurally characterized as actinomycin D (act-D) by mass spectrometric and nuclear magnetic resonance analyses Plackett-Burman design (PBD) and response surface methodology (RSM) were applied in order to optimize the medium formulation for the production of this bioactive metabolite. By PBD experiments, NaNO3, K2HPO4 and initial pH value were selected as significant variables affecting the metabolite production. Central Composite Design (CCD) showed that adjustment of the fermentative medium at pH 8.25, K2HPO4 at 0.2 gL-1 and NaNO3 at 3.76 gL-1 were the values suiting the production of act-D. Moreover, the results obtained by the statistical approach were confirmed by act-D detection using the HPLC equipped with a diode array detector and coupled online with electrospray-mass spectrometry (ESIMS) technique. act-D production was highly stimulated, obtaining a good yield (656.46 mgL-1) which corresponds to a 58.56% increase compared with the non-optimized conditions and data from LC-ESIMS technique efficiently confirmed the forecast from RSM.

Streptomyces thermoviolaceus SRC3 strain as a novel source of the antibiotic adjuvant streptazolin: A statistical approach toward the optimized production.

Streptomyces thermoviolaceus SRC3, a newly isolated actinobacterial strain from Algerian river sediments, exhibited a broad activity against various bacterial and yeast human pathogens (Salmonella Typhi ATCC 14028, Vibrio cholerae ATCC 14035, MRSA ATCC 43300 and Candida albicans ATCC 10231). The strain SRC3 was selected from thirty nine actinobacterial isolates and identified as S. thermoviolaceus based on morphology, cultural properties, physiological analyses and 16S rRNA gene sequencing. Culture parameters for the antibiotic production were optimized by sequential statistical strategy including Plackett-Burman design (PBD) and Response Surface Methodology (RSM). In PBD experiments, KCl, K2HPO4, MgSO4·7H2O, pH value and incubation time emerged as the most significant in affecting the output of antimicrobial activities. These factors were further optimized using Central Composite Design (CCD). The best achieved conditions were: KCl (0.01%), K2HPO4 (0.1%), MgSO4·7H2O (0.02%) and 9 days incubation for anti-S. Typhi compounds, KCl (0.051%), MgSO4·7H2O (0.05%) and 5 days incubation for C. albicans inhibitors. The metabolite responsible for the bioactivities was purified, structurally characterized (by NMR, MS, UV and IR analyses) and identified as streptazolin, recently reported as a promising antibiotic adjuvant.

Antibacterial polyketides from the marine alga-derived endophitic Streptomyces sundarbansensis: a study on hydroxypyrone tautomerism.

Polyketide 13 [=2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2- propylchroman-4-one] and three related known compounds 7, 9 and 11 were obtained and structurally characterized from Streptomyces sundarbansensis strain, an endophytic actinomycete isolated from the Algerian marine brown algae Fucus sp. Compound 13 was obtained as the major metabolite from optimized culture conditions, by using Agar state fermentation. Due to tautomeric equilibrium, 13 in CD(3)OD solution was able to incorporate five deuterium atoms, as deduced by NMR and ESI-MS/MS analysis. The 2-hydroxy-γ-pyrone form was established for these metabolites based on the comparison of their experimental IR spectra with the DFT calculated ones, for both the corresponding 4-hydroxy-α-pyrone and 2-hydroxy-γ-pyrone forms. During antibacterial evaluation, compound 13 stood out as the most active of the series, showing a selective activity against the gram positive pathogenic methicillin-resistant S. aureus (MRSA, MIC = 6 µΜ), with a bacteriostatic effect.