High-throughput 16S rRNA gene-based amplicon sequencing reveals the functional divergence of halophilic bacterial communities in the Suaeda salsa root compartments on the eastern coast of China

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 942, P. 173775 - 173775

Published: June 5, 2024

Language: Английский

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AptERA 2 targets ERA from Staphylococcus aureus and limits GTP hydrolysis

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Ribosome assembly is a multistep process that ensures functional ribosome structure. The molecular mechanism ribosome­associated GTPases (RA­GTPases) use to enhance accuracy, remains largely be elucidated. Here, we systematic evolution of ligands by exponential enrichment (SELEX), followed sequencing, comprehensive bioinformatics analysis, and biochemical characterization identify aptamers target the RA-GTPase ERA Staphylococcus aureus. ELONA thermophoresis assays show Apt_ERA 2 interaction with in 200 nM range affinity, displays high level specificity, depends on Docking suggests interacts protein's KH domain, consistent aptamer's similarities helix 45 16S rRNA. did not interact similar RbgA, conserved at GTPase core but lacking confirming aptamer recognizes binds domain ERA. This leads significant reduction 30S-dependent GTP hydrolysis, indicative allosteric modulation enzyme activity or limiting 3’ end rRNA rather than directly blocking binding. Altogether, this work highlights versatility as tools understand complex processes biogenesis further, offering new insights into bacterial protein synthesis mechanisms.

Language: Английский

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Artesunate Perturbs GTP Binding of the Conserved GTPase Obg Thereby Alleviating Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen that causes various secondary infections among hospital-associated patients. The challenging to treat due its resistance a wide spectrum of antibiotics, including the last-resort antibiotic vancomycin and newly developed drugs, such as linezolid daptomycin. While invention entirely new drugs combat MRSA infection seems almost impossible, potentiating efficacy conventional antibiotics critical. Our article explores novel application antimalarial drug artesunate, which enhances cefoxitin in treating infections. We focused on ObgSa, conserved GTPase MRSA, found artesunate selectively binds GTP-binding pocket. further evaluated activity metal dependence (specifically, Mg2+) this GTPase. In silico analysis identified several threonine residues essential for GTP binding, were subsequently mutated assess their role binding. As shown analysis, these mutations significantly impacted both binding hydrolysis functions ObgSa. Notably, also crucial within domain. When effect was assessed, competitively inhibited This result manifested reduced tolerance, disruption biofilms, decrease persister cells─critical factors chronic summary, our research presents innovative strategy antimicrobial through highlighting potential effectiveness eradicating

Language: Английский

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Nucleic acid-binding KH domain proteins influence a spectrum of biological pathways including as part of membrane-localized complexes

Journal of Structural Biology X, Journal Year: 2024, Volume and Issue: 10, P. 100106 - 100106

Published: June 28, 2024

K-Homology domain (KH domain) proteins bind single-stranded nucleic acids, influence protein–protein interactions of that harbor them, and are found in all kingdoms life. In concert with other functional protein domains KH contribute to a variety critical biological activities, often within higher order machineries including membrane-localized complexes. Eukaryotic linked developmental processes, morphogenesis, growth regulation, their aberrant expression is associated cancer. Prokaryotic involved integral cellular activities cell division translocation. prokaryotic share structural features, but differentiated based on organizations. this review, we explore the structure/function relationships known examples proteins, highlight cases which they function or at membrane surfaces. We also summarize bacterial virulence pathogenesis. conclude article by discussing prospective research avenues could be pursued better investigate largely understudied category.

Language: Английский

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Knockout Mouse Studies Show Mitochondrial CLPP Peptidase and CLPX Unfoldase to Act in Matrix Condensates Near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production

Published: April 26, 2024

LONP1 is the principal AAA+ unfoldase and bulk protease in mitochondrial matrix, so its deletion causes embryonic lethality. The CLPX peptidase CLPP also act conspicuously during stress periods, but their substrates are poorly defined. Mammalian triggers infertility, deafness, growth retardation, cGAS-STING activated cytosolic innate immunity. mutations impair heme biosynthesis heavy metal homeostasis. conserved from bacteria to human, despite secondary role for proteolysis. Based on recent proteomic-metabolomic evidence knockout mice patient cells, we propose that acts phase-separated ribonucleoprotein granules, multi-enzyme condensates, near inner membrane, as first-aid system. Trimming within assemblies, rescues stalled processes mitoribosomes, RNA granules nucleoids, D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding maximizes PLP-dependent delta-transamination, malformed nascent peptides. Overall, actions occur with multivalent or hydrophobic interactions, separated aqueous phase. Thus, CLPXP matrix compartment-selective, like peptidases MPP at precursor import pores, m-AAA i-AAA either IMM face, PARL IMM, OMA1/HTRA2 intermembrane space.

Language: Английский

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The stringent response is strongly activated in the antibiotic producing strain, Streptomyces coelicolor

Research in Microbiology, Journal Year: 2023, Volume and Issue: 175(4), P. 104177 - 104177

Published: Dec. 28, 2023

S. lividans and coelicolor are phylogenetically closely related strains with different abilities to produce the same specialized metabolites. Previous studies revealed that strong antibiotic producer, coelicolor, had a lower ability assimilate nitrogen phosphate than weak lividans, this resulted into growth rate. A comparative proteomic dataset was used establish consequences of these nutritional stresses on abundance proteins translational apparatus strains, grown in low high availability. Our study most were less abundant whereas it opposite for ET-Tu 3 TrmA-like methyltransferase. The expression latter being known be under positive control stringent response other ribosomal is its negative control, indicated occurrence activation coelicolor. Furthermore, more proficiency limitation suggesting phosphate, also shown trigger RelA expression, contributes induction response.

Language: Английский

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Knockout Mouse Studies Show That Mitochondrial CLPP Peptidase and CLPX Unfoldase Act in Matrix Condensates near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production

Genes, Journal Year: 2024, Volume and Issue: 15(6), P. 694 - 694

Published: May 27, 2024

LONP1 is the principal AAA+ unfoldase and bulk protease in mitochondrial matrix, so its deletion causes embryonic lethality. The CLPX peptidase CLPP also act especially during stress periods, but their substrates are poorly defined. Mammalian triggers infertility, deafness, growth retardation, cGAS-STING-activated cytosolic innate immunity. mutations impair heme biosynthesis heavy metal homeostasis. conserved from bacteria to humans, despite secondary role proteolysis. Based on recent proteomic-metabolomic evidence knockout mice patient cells, we propose that acts phase-separated ribonucleoprotein granules multi-enzyme condensates as first-aid systems near inner membrane. Trimming within assemblies, rescues stalled processes mitoribosomes, RNA nucleoids, D-foci-mediated degradation of toxic double-stranded mtRNA/mtDNA. Unfolding condensates, maximizes PLP-dependent delta-transamination malformed nascent peptides. Overall, actions occur with multivalent or hydrophobic interactions, separated aqueous phase. Thus, CLPXP matrix compartment-selective, other peptidases: MPPs at precursor import pores, m-AAA i-AAA either IMM face, PARL IMM, OMA1/HTRA2 intermembrane space.

Language: Английский

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Comprehensive bioinformatics analysis identifies biomarkers for cardiovascular risk in end-stage renal diseases

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Objective End-stage renal disease (ESRD) can increase the risk of cardiovascular (CV). We aimed to investigate pathways and mechanisms associated with potential protective genes linked CV (CVP). Methods conducted a systematic bioinformatics analysis using publicly available datasets from Gene Expression Omnibus (GEO). Differentially expressed (DEGs) were identified in patients ESRD without arrhythmia stringent statistical criteria. Functional enrichment analyses performed Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) elucidate biological roles these DEGs. Receiver Operating Characteristic (ROC) curve was used evaluate diagnostic performance biomarkers for prediction. Results Our revealed distinct set DEGs compared those arrhythmia. GO KEGG pathway indicated that involved key processes relevant disorders function, including wound healing, platelet activation, fluid-level regulation. Moreover, this study four downregulated (ABLIM3, TREML1, VCL, AVPR1A) two upregulated (BHLHA15 FZD8), which exhibited significant alterations expression levels, some showing robust discriminatory power, as evidenced by high Area Under Curve (AUC) values ROC predicting risks. Conclusion This panel (including miRNA an unknown gene) plasma may serve promising patients. These findings provide foundation future validation studies at integrating into clinical practice improve stratification management ESRD.

Language: Английский

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