Antibacterial and antibiofilm properties of two cyclic dipeptides produced by a new desert Streptomyces sp. HG-17 strain against multidrug-resistant pathogenic bacteria.

INTRODUCTION: The emergence of multidrug-resistant bacteria and biofilms requires discovering new antimicrobial agents from unexplored environments. OBJECTIVES: This study aims to isolate and characterize a new actinobacterial strain from the Hoggar Mountains in southern Algeria and evaluate its ability to produce bioactive molecules with potential antibacterial and antibiofilm activities. METHODS: A novel halotolerant actinobacterial strain, designated HG-17, was isolated from the Hoggar Mountains, and identified based on phenotypic characterizations, 16S rDNA sequence analysis, and phylogenetic analysis. The antibacterial and antibiofilm activities of the strain were assessed, and the presence of biosynthetic genes (PKS-I and NRPS) was confirmed. Two active compounds, HG-7 and HG-9, were extracted butanol solvent, purified by HPLC, and their chemical structures were elucidated using ESI mass spectrometry and NMR spectroscopy. RESULTS: The strain HG-17 was identified as Streptomyces purpureus NBRC with 98.8% similarity. It exhibited strong activity against multidrug-resistant and biofilm-forming bacteria. The two purified active compounds, HG-7 and HG-9, were identified as cyclo-(d-cis-hydroxyproline-l-phenylalanine) and cyclo-(l-prolone-l-tyrosine), respectively. The minimum inhibitory concentrations (MICs) of HG-7 and HG-9 ranged from 3 to 15 µg/mL, comparable to the MICs of tetracycline (8 to 15 µg/mL). Their minimum biofilm inhibitory concentration (MBIC 50%) showed good inhibition from 48.0 to 52.0% at concentrations of 1 to 7 µg/mL against the tested bacteria. CONCLUSION: This is the first report of cyclo-(d-cis-hydroxyproline-l-phenylalanine) and cyclo-(l-prolone-l-tyrosine) antibiotics from S. purpureus and their anti-multi-drug-resistant and biofilm-forming bacteria. These results indicate that both antibiotics could be used as effective therapeutics to control infections associated with multidrug-resistant bacteria.

A New Saharan Strain of Streptomyces sp. GSB-11 Produces Maculosin and N-acetyltyramine Active Against Multidrug-Resistant Pathogenic Bacteria.

Multi-resistant bacterial pathogens are a major public health problem for treating nosocomial infections owing to their high resistance to antibiotics. The objective of this research was to characterize the bioactive molecules secreted by a novel moderately halophilic actinobacterium strain, designated GSB-11, exhibiting a strong antagonistic activity against several multidrug-resistant pathogenic bacteria. This potential strain was identified by phenotypic, genotypic (16S rRNA), and phylogenetic analyses. GSB-11 was related to "Streptomyces acrimycini" NBRC 12736 T with 99.59% similarity. Molecular screening by PCR assay demonstrated that the strain possesses two biosynthetic genes coding for NRPS and PKS-II. Two active compounds GSB11-6 and GSB11-7 were extracted from the cell-free culture supernatant of Bennett medium and purified using reversed-phase HPLC. According to spectrometric (mass spectrum) and spectroscopic (1H NMR, 13C NMR, 1H-1H COSY, and 1H-13C HMBC) spectra analyses, the compounds GSB11-6 and GSB11-7 were identified to be maculosin and N-acetyltyramine, respectively. Their minimum inhibitory concentrations (MIC) revealed interesting values against certain multidrug-resistant pathogenic bacteria. They were between 5 and 15 mg/mL for GSB11-6, 10 and 30 mg/mL for GSB11-7. To our best knowledge, this is the first study of these active substances isolated from "Streptomyces acrimycini" showing an interesting antibacterial activity. Therefore, these essential compounds could be candidates for future research against multidrug-resistant bacteria.

Streptomyces sp. AT37 isolated from a Saharan soil produces a furanone derivative active against multidrug-resistant Staphylococcus aureus.

A novel actinobacterium strain, named AT37, showed a strong activity against some multidrug-resistant Staphylococcus aureus, including methicillin-resistant S. aureus MRSA ATCC 43300, other clinical isolates of MRSA and vancomycin resistant S. aureus VRSA S1. The strain AT37 was isolated from a Saharan soil by a dilution agar plating method using chitin-vitamin agar medium supplemented with rifampicin. The morphological and chemical studies indicated that this strain belonged to the genus Streptomyces. Its 16S rRNA gene sequence was determined and a database search indicated that it was closely associated with the type strain of Streptomyces novaecaesareae NBRC 13368T with 99.6% of similarity. However, the comparison of the morphological and the physiological characteristics of the strain with those of the nearest species showed significant differences. The strain AT37 secreted the antibiotic optimally during mid-stationary phase of growth. One active compound (AT37-1) was extracted from the culture broth with dichloromethane, separated on silica gel plates and purified by HPLC. Based on spectroscopic analysis of UV-Visible, infrared, and 1H and 13C NMR spectra and spectrometric analysis, the chemical structure of the compound AT37-1 was identified as 5-[(5E,7E,11E)-2,10-dihydroxy-9,11-dimethyl-5,7,11-tridecatrien-1-yl]-2-hydroxy-2-(1-hydroxyethyl)-4-methyl-3(2H)-furanone. Minimum inhibitory concentrations and minimum biofilm inhibitory concentration (MBIC50) of this compound showed significant activity against multidrug-resistant S. aureus with 15-30 and 10-15 µg/mL, respectively.

Nocardiopsis and Saccharothrix genera in Saharan soils in Algeria: isolation, biological activities and partial characterization of antibiotics.

Twenty-five soil samples were collected in the Algerian Sahara and analyzed to isolate rare actinomycetes. Eighty-six isolates with the same Nocardiopsis or Saccharothrix morphology were isolated on humic-vitamin B agar medium using dilution techniques and several antibiotics as selective agents. Certain of these antibiotics seemed to be very selective for some phenotypes. Morphological and chemotaxonomic characteristics led to identifying 54 isolates belonging to the Nocardiopsis genus and 32 isolates belonging to the Saccharothrix genus. An assessment of the antimicrobial properties of the isolates showed activities against Gram-positive bacteria, fungi and yeasts. Saccharothrix isolates possessed better antifungal activity than Nocardiopsis. One of them, labeled SA 103, was therefore selected for identification of its antifungal antibiotic activities. Production of overall antifungal and antibacterial activities was checked on the complex medium ISP2 and a synthetic medium (SM) that contains glucose or starch as carbon source, and ammonium or nitrate as nitrogen source. The SM medium containing ammonium sulfate (0.2%), supplemented with starch (0.5%) and yeast extract (0.3%), was retained for production of antibiotics. Active substances were purified by a G25-80 Sephadex column and reverse phase HPLC. Two pure substances were obtained and named ZA01 and ZA02; they were characterized on the basis of combined data resulting from chemical tests, UV visibile and IR spectra and mass spectrometry. The two antibiotics were found to be related and were partially characterized as nucleotidic or nucleosidic antibiotics. Their structures consisted of a chain of three sugar units linked to an aromatic base containing a phosphate residue.

New dithiolopyrrolone antibiotics from Saccharothrix sp. SA 233. I. Taxonomy, fermentation, isolation and biological activities.

Three new natural antibacterial and antifungal dithiolopyrrolone antibiotics were isolated along with the known iso-butyropyrrothine and thiolutine from the fermentation broth of an actinomycete strain which was isolated from a saharian palm grove soil collected at Adrar, south Algeria. The strain was identified as Saccharothrix sp. The three new antibiotics exhibited broad antimicrobial activity against gram-positive bacteria, yeasts and fungi in vitro.

Isolation and partial characterization of antimicrobial compounds from a new strain Nonomuraea sp. NM94.

An actinomycete strain NM94 was isolated from a Saharan soil sample by a dilution agar plating method using chitin-vitamins B medium supplemented with penicillin. The strain presented the morphological and chemical characteristics of the genus Nonomuraea. On the basis of 16S rDNA analysis and physiological tests, this isolate was found to be quite different from the known species of Nonomuraea and might be new. The strain NM94 secreted several antibiotics on yeast extract malt extract glucose medium that were active against some Gram-positive bacteria, yeast, and fungi. The antibiotics were extracted with dichloromethane and detected by bioautography on silica gel plates using Mucor ramannianus and Bacillus subtilis as the test organisms. Among these antibiotics, a complex called 94A showed interesting antifungal activity. It was selected and purified by reverse-phase HPLC. This complex was composed of five compounds. Spectroscopic studies by infrared, mass, and (1)H NMR of the compounds were carried out. Initial results showed that these molecules differed from the known antibiotics produced by other Nonomuraea species.