Genomic and Phenotypic Characterization of sp. nov., Amicetin-Producing Actinobacteria Isolated from Bamboo Rhizospheric Soil.

In our large-scale search for antimicrobial-producing bacteria, we isolated an actinomycete strain from rhizospheric soil of . The strain designated BP-8 showed noticeable antibacterial activity. BP-8 was subjected to a whole-genome analysis via a polyphasic taxonomy approach, and its antibacterial metabolite was identified by HRLS-MS.

Novel Selectable Marker Sesquiterpenoid Antibiotic Pentalenolactone.

Antibiotic resistance has been and remains a major problem in our society. The main solution to this problem is to search and study the mechanisms of antibiotic action. Many groups of secondary metabolites, including antimicrobial ones, are produced by the phylum.

Synthesis and Antibacterial Activity of New 6″-Modified Tobramycin Derivatives.

Aminoglycosides are one of the first classes of natural antibiotics which have not lost relevance due to their broad spectrum of action against Gram-positive, Gram-negative bacteria and mycobacteria. The high growth rate of antimicrobial resistance (AMR) together with the severe side effects of aminoglycosides increase the importance of developing improved semisynthetic derivatives. In this work, we proposed a synthetic route to new tobramycin derivatives modified at the 6″-position with aminoalkylamine or guanidinoalkylamine residues.

Mining Translation Inhibitors by a Unique Peptidyl-Aminonucleoside Synthetase Reveals Cystocin Biosynthesis and Self-Resistance.

Puromycin (Puro) is a natural aminonucleoside antibiotic that inhibits protein synthesis by its incorporation into elongating peptide chains. The unique mechanism of Puro finds diverse applications in molecular biology, including the selection of genetically engineered cell lines, in situ protein synthesis monitoring, and studying ribosome functions. However, the key step of Puro biosynthesis remains enigmatic.

Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.

Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome.

The Synthesis and Analysis of the Cytotoxicity of AlO-Supported Silver Nanoparticles Prepared by the Plasma Chemical Process Initiated by Pulsed MW Radiation in the AlO-Ag Powder Mixtures.

An original plasma chemical process initiated by microwave discharge in a mixture of metal and dielectric powders was applied to prepare specific materials, which consisted of microsized spherical particles of aluminum oxide covered with silver nanoparticles. The prepared materials are highly uniform in shape, size distribution, and composition. Their cytotoxicity was investigated using the human cell lines MCF7, HEK293T, A549, and VA-13 and the bacterial strains JW5503 (ΔtolC) and K12.

Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents.

Antimicrobial peptides (AMPs) have recently attracted attention as promising antibacterial agents capable of acting against resistant bacterial strains. In this work, an approach was applied, consisting of the conjugation of a peptide related to the sequences of bactenecin 7 (Bac7) and oncocin (Onc112) with the alkyl(triphenyl)phosphonium (alkyl-TPP) fragment in order to improve the properties of the AMP and introduce new ones, expand the spectrum of antimicrobial activity, and reduce the inhibitory effect on the eukaryotic translation process. Triphenylphosphonium (TPP) derivatives of a decapeptide RRIRPRPPYL were synthesized.

AgO-Containing Biocidal Interpolyelectrolyte Complexes on Glass Surfaces-Adhesive Properties of the Coatings.

Biocidal coatings are of great interest to the healthcare system. In this work, the biocidal activity of coatings based on a complex biocide containing polymer and inorganic active antibacterial components was studied. Silver oxide was distributed in a matrix of a positively charged interpolyelectrolyte complex (IPEC) of polydiallyldimethylammonium chloride (PDADMAC) and sodium polystyrene sulfonate (PSS) using ultrasonic dispersion, forming nanoparticles with an average size of 5-6 nm.

Bioprospecting for the soil-derived actinobacteria and bioactive secondary metabolites on the Western Qinghai-Tibet Plateau.

Introduction: The increase in incidence of multidrug-resistant bacteria and the inadequacy of new antimicrobial drugs have led to a widespread outbreak of bacterial antimicrobial resistance. To discover new antibiotics, biodiversity, and novelty of culturable actinobacteria dwelled in soil of the Western Qinghai-Tibet Plateau were investigated. By integrating antibacterial assay with omics tools, sp.

Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents.

In order to obtain antimicrobial compounds with improved properties, new conjugates comprising two different biologically active agents within a single chimeric molecule based on chloramphenicol (CHL) and a hydrophobic cation were synthesized and studied. Chloramphenicol amine (CAM), derived from the ribosome-targeting antibiotic CHL, and the plant isoquinoline alkaloid berberine (BER) are connected by alkyl linkers of different lengths in structures of these conjugates. Using competition binding, double reporter system, and toeprinting assays, we showed that synthesized CAM-Cn-BER compounds bound to the bacterial ribosome and inhibited protein synthesis like the parent CHL.

A New Albomycin-Producing Strain of subsp. May Provide Protection for Ants .

There are several well-studied examples of protective symbiosis between insect host and symbiotic actinobacteria, producing antimicrobial metabolites to inhibit host pathogens. These mutualistic relationships are best described for some wasps and leaf-cutting ants, while a huge variety of insect species still remain poorly explored. For the first time, we isolated actinobacteria from the harvester ant and evaluated the isolates' potential as antimicrobial producers.

Conjugates of Desmycosin with Fragments of Antimicrobial Peptide Oncocin: Synthesis, Antibacterial Activity, Interaction with Ribosome.

Design and synthesis of conjugates consisting of the macrolide antibiotic desmycosin and fragments of the antibacterial peptide oncocin were performed in attempt to develop new antimicrobial compounds. New compounds were shown to bind to the E. coli 70S ribosomes, to inhibit bacterial protein synthesis in vitro, as well as to suppress bacterial growth.

Mechanism-Based Approach to New Antibiotic Producers Screening among Actinomycetes in the Course of the Citizen Science Project.

Since the discovery of streptomycin, actinomycetes have been a useful source for new antibiotics, but there have been diminishing rates of new finds since the 1960s. The decreasing probability of identifying new active agents led to reduced interest in soil bacteria as a source for new antibiotics. At the same time, actinomycetes remain a promising reservoir for new active molecules.

Dispirooxindole-β-Lactams: Synthesis via Staudinger Ketene-Imine Cycloaddition and Biological Evaluation.

In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against strain LPTD.

Biological evaluation and spectral characterization of a novel tetracenomycin X congener.

The aromatic polyketide tetracenomycin X (TcmX) was recently found to be a potent inhibitor of protein synthesis; its binding site is located in a unique locus within the tunnel of the large ribosomal subunit. The distinct mode of action makes this relatively narrow class of aromatic polyketides promising for drug development in the quest to prevent the spread of drug-resistant pathogens. Here we report the isolation and structure elucidation of a novel natural tetracenomycin X congener - 6-hydroxytetraceonomycin X (6-OH-TcmX).

Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents.

In the current work, in continuation of our recent research, we synthesized and studied new chimeric compounds, including the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly reduce membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP in bacterial ribosomes differs from that of CHL.

Binding and Action of Triphenylphosphonium Analog of Chloramphenicol upon the Bacterial Ribosome.

Chloramphenicol (CHL) is a ribosome-targeting antibiotic that binds to the peptidyl transferase center (PTC) of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving the properties of this inhibitor, we explored ribosome binding and inhibitory properties of a semi-synthetic triphenylphosphonium analog of CHL-CAM-C4-TPP. Our data demonstrate that this compound exhibits a ~5-fold stronger affinity for the bacterial ribosome and higher potency as an in vitro protein synthesis inhibitor compared to CHL.

Nybomycin inhibits both types of DNA gyrase - fluoroquinolone-sensitive and fluoroquinolone-resistant.

Bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, are targets of many antibiotics including fluoroquinolones (FQs). Unfortunately, a number of bacterial species easily acquire resistance to FQs by mutations in either DNA gyrase or topoisomerase IV genes. The emergence of resistant pathogenic strains is a global problem in healthcare, therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery.

Beilunmycin, a new virginiamycins antibiotic from mangrove-derived sp. 2BBP-J2 and the antibacterial activity by inhibiting protein translation.

One new virginiamycin derivative, 'beilunmycin' (), and three known virginiamycin antibiotics, 16-hydroxy-virginiamycin M1 (), virginiamycin M2 (), and virginiamycin M1 (), were isolated from the culture of a mangrove-derived endophytic sp. 2BBP-J2. The structures were characterized on the basis of their spectroscopic data, and the absolute configuration of was established by ECD calculations.

Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel.

The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel.

Substituted Furanocoumarins as Novel Class of Antibacterial Translation Inhibitors.

Introduction: A variety of organic compounds has been reported to have antibacterial activity. However, antimicrobial resistance is one of the main problems of current anti-infective therapy, and the development of novel antibacterials is one of the main challenges of current drug discovery.

Methods: Using our previously developed dual-reporter High-Throughput Screening (HTS) platform, we identified a series of furanocoumarins as having high antibacterial activity.

Nybomycin-producing Streptomyces isolated from carpenter ant Camponotus vagus.

A novel strain of Actinomycetes was isolated from the body of an ant (Camponotus vagus Scopoli) and its genetic and morphological properties were characterized. The 16S rDNA gene sequence analysis of the isolate revealed its high phylogenetic relationship with type strains of Streptomyces violaceochromogenes NBRC 13100. As a result of antimicrobial activity assessment, it was found that the fermentation broth of the isolated strain both inhibited the growth and induced the SOS response in E.