A5060425578- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Calcium Carbonate Crystallization and Inhibition
- Antimicrobial Resistance in Staphylococcus
- Bacterial Genetics and Biotechnology
- Paleontology and Stratigraphy of Fossils
- Minerals Flotation and Separation Techniques
- Toxin Mechanisms and Immunotoxins
- Geochemistry and Elemental Analysis
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Veterinary medicine and infectious diseases
- Geomagnetism and Paleomagnetism Studies
- Monoclonal and Polyclonal Antibodies Research
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Antifungal resistance and susceptibility
- Physiological and biochemical adaptations
- vaccines and immunoinformatics approaches
- Viral Infections and Immunology Research
- Microbial Natural Products and Biosynthesis
- Molecular Junctions and Nanostructures
- Metal Extraction and Bioleaching
- Marine Biology and Ecology Research
- Microbial Metabolism and Applications
Weizmann Institute of Science
2015-2025
The emergence of bacterial multidrug resistance to antibiotics threatens cause regression the preantibiotic era. Here we present crystal structure large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with known linezolid telithromycin, as well new, highly potent pleuromutilin derivative, BC-3205. These structures shed light on specific structural motifs S. aureus ribosome binding modes aforementioned antibiotics. Moreover, by...
The increasing appearance of pathogenic bacteria with antibiotic resistance is a global threat. Consequently, clinically available potent antibiotics that are active against multidrug resistant pathogens becoming exceedingly scarce. Ribosomes main target for antibiotics, and hence an objective novel drug development. Lefamulin, semi-synthetic pleuromutilin compound highly multi-resistant pathogens, promising currently in phase III trials the treatment community-acquired bacterial pneumonia...
Antimicrobial resistance within a wide range of pathogenic bacteria is an increasingly serious threat to global public health. Among these are the highly resistant, versatile and possibly aggressive bacteria, Staphylococcus aureus. Lincosamide antibiotics were proved be effective against this pathogen. This small, albeit important group mostly active Gram-positive but also used selected Gram-negative anaerobes protozoa. S. aureus lincosamides can acquired by modifications and/or mutations in...
Pigmentation plays a vital role in the survival of organisms, supporting functions such as camouflage, communication, and mate attraction. In vertebrates, these are mediated by specialized pigment cells known chromatophores which, uric acid crystal-forming leucophores remain least understood, with little about their molecular mechanisms. A key question cell biology is whether different crystal chemistries require distinct pathways, or similar cellular processes drive formation diverse...
Abstract The clinical use of the antibiotic erythromycin (ery) is hampered owing to spread resistance genes that are mostly mutating rRNA around ery binding site at entrance protein exit tunnel. Additional effective mechanisms include deletion or insertion mutations in ribosomal uL22, which lead alterations tunnel shape, located 16 Å away from drug’s site. We determined cryo-EM structures Staphylococcus aureus 70S ribosome, and its bound complex with a two amino acid mutation ß hairpin loop,...
Organisms evolve mechanisms that regulate the properties of biogenic crystals to support a wide range functions, from vision and camouflage communication thermal regulation. Yet, mechanism underlying formation diverse intracellular remains enigmatic. Here we unravel biochemical control over crystal morphogenesis in zebrafish iridophores. We show chemical composition determines their shape, particularly through ratio between nucleobases guanine hypoxanthine. reveal these variations are...
ABSTRACT An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in 70S ribosomes from a clinical isolate Staphylococcus aureus . This high-resolution structural information demonstrated that single amino acid deletion ribosomal protein uL3 confers despite being located 24 Å away binding pocket peptidyl-transferase center. The mutation induces cascade allosteric rearrangements rRNA ultimately results alteration site....
Resistance to antibiotics has become a major threat modern medicine. The ribosome plays fundamental role in cell vitality by the translation of genetic code into proteins; hence, it is target for clinically useful antibiotics. We report here cryo-electron microscopy structures pathogenic aminoglycoside (AG)-resistant Pseudomonas aeruginosa strain, as well nonresistance strain isolated from cystic fibrosis patient. structural studies disclosed defective complex formation due conformational...
Controlling the morphology of crystalline materials is challenging, as crystals have a strong tendency toward thermodynamically stable structures. Yet, organisms form with distinct morphologies, such plate-like guanine produced by many terrestrial and aquatic species for light manipulation. Regulation crystal morphogenesis was hypothesized to entail physical growth restriction surrounding membrane, combined fine-tuned interactions between organic molecules growing crystal. Using...
Pigmentation plays a vital role in the survival of organisms, supporting functions such as camouflage, communication, and mate attraction. In vertebrates, these are mediated by specialized pigment cells known chromatophores which, uric acid crystal–forming leucophores remain least understood, with little about their molecular mechanisms. A key question cell biology is whether different crystal chemistries require distinct pathways, or similar cellular processes drive formation diverse...
Significance Resistance to antibiotics poses a serious threat in contemporary medicine. Avilamycin and evernimicin, polysaccharide belonging the orthosomycin family, possess inhibitory activity against multidrug-resistant pathogenic strains of Enterococci , Staphylococci other Streptococci gram-positive bacteria by paralyzing ribosomes function protein biosynthesis. The crystal structures large ribosomal subunit from eubacteria Deinococcus radiodurans complex with avilamycin evernimicin...
Abstract Metal sulfides are a common group of extracellular bacterial biominerals. However, only few cases intracellular biomineralization reported in this group, mostly limited to greigite (Fe 3 S 4 ) magnetotactic bacteria. Here, previously unknown periplasmic copper sulfide produced by the bacterium Desulfamplus magnetovallimortis strain BW‐1, species known mineralize and magnetite O cytoplasm is reported. BW‐1 produces hundreds spherical nanoparticles, composed 1–2 nm substructures...
Biogenic crystals present a variety of complex morphologies that form with exquisite fidelity. In the case intricate coccoliths, calcite produced by marine algae, only single set crystallographic facets is utilized. It unclear which growth process can merge this simple habit species-specific architectures. Here, suite state-of-the-art electron microscopies used to follow both trajectories ex situ, and cellular environment in species Emiliania huxleyi. shown crystal alternates between space...
Many organisms orchestrate the controlled precipitation of minerals. This physiological process takes place at ambient conditions, using soluble ions as building blocks. A widespread strategy for such crystallization processes is a multistep route, where initial phase metastable and gradually transforms into mature mineral phase. Even though maturation these intermediate phases has been intensively studied, it remains unclear how initial, far from equilibrium can form within cellular...
Macrolides have been effective clinical antibiotics for over 70 years. They inhibit protein biosynthesis in bacterial pathogens by narrowing the nascent exit tunnel ribosome. The macrolide class of natural products consist a macrolactone ring linked to one or more sugar molecules. Most macrolides used currently are semi-synthetic erythromycin derivatives, composed 14- 15-membered ring. Rapidly emerging resistance is among most urgent global health challenges, which render many ineffective,...
The ribosome, a multicomponent assembly consisting of RNA and proteins, is pivotal macromolecular machine that translates the genetic code into proteins. large ribosomal subunit rRNA helix 68 (H68) key element in protein synthesis process, as it coordinates coupled movements actors involved translocation, including tRNAs L1 stalk. Examination cryo-electron microscopy (cryo-EM) structures ribosomes incubated for various time durations at physiological temperatures led to identification...
Many animals exhibit remarkable colors produced by the constructive interference of light reflected from arrays intracellular guanine crystals. These systems are utilized for various purposes, including vision, camouflage, communication, and thermal regulation. Each crystal forms within a membrane-bound organelle called an iridosome, where precise control over formation occurs. While presence crystals in iridosomes is well-documented, mechanisms facilitating accumulation water-insoluble...
Metal sulfides are a common group of extracellular bacterial biominerals. Only few cases intracellular biomineralization have been reported in this group, mostly limited to greigite (Fe3S4) magnetotactic bacteria. Here, we report the but periplasmic copper sulfide by bacterium Desulfamplus magnetovallimortis (strain BW-1) that is known mineralize and magnetite (Fe3O4) cytoplasm. BW-1 produces hundreds spherical nanoparticles, composed 1-2 nm substructures poorly crystalline hexagonal remains...