Discovery of novel antibacterial agent for the infected wound treatment: all-hydrocarbon stapling optimization of LL-37

Theranostics, Journal Year: 2024, Volume and Issue: 14(3), P. 1181 - 1194

Published: Jan. 1, 2024

Rationale: Antimicrobial peptide LL-37 has been recognized as a favorable alternative to antibiotics due its broad antibacterial spectrum, low resistance development and diverse biological activities.However, high manufactory cost, poor proteolytic stability, unpredictable cytotoxicity seriously hindered medical translation.Methods: To push the frontiers of clinical application, all-hydrocarbon stapling strategy was exploited here for structural modification KR-12, core minimal fragment LL-37.Results: Based on library KR-12 derivatives that designed synthesized be stapled at positions either i, i+4 or i+7, structure activity relationship investigated.Among them, KR-12(Q5, D9) with glutamine aspartic acid residues displayed increased helical content positive charge.The reinforced α-helical conformation not only protected it from hydrolysis but also improved efficacy via effective membrane perturbation anti-inflammatory compact LPS binding.Besides, charge endowed an enhanced therapeutic index.On infected wound mouse model, demonstrated eliminate bacteria promote closure regeneration effectively. Conclusion:Overall, proven lay foundation future agents.KR-12(Q5, could serve lead compound treatment bacterial infections.

Language: Английский

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Effects of UV-aged tire wear particles (TWPs) on soil microorganisms: microbial community, microbial metabolism, cell defense and repair, and transmission of ARGs

Journal of environmental chemical engineering, Journal Year: 2025, Volume and Issue: 13(2), P. 115624 - 115624

Published: Jan. 28, 2025

Language: Английский

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Effects of decabromodiphenyl ethane (DBDPE) exposure on soil microbial community: Nitrogen cycle, microbial defense and repair and antibiotic resistance genes transfer

Journal of Environmental Management, Journal Year: 2025, Volume and Issue: 376, P. 124503 - 124503

Published: Feb. 15, 2025

Language: Английский

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Non-antibiotic compounds associated with humans and the environment can promote horizontal transfer of antimicrobial resistance genes

Critical Reviews in Microbiology, Journal Year: 2023, Volume and Issue: 50(6), P. 993 - 1010

Published: July 18, 2023

Horizontal gene transfer plays a key role in the global dissemination of antimicrobial resistance (AMR). AMR genes are often carried on self-transmissible plasmids, which shared amongst bacteria primarily by conjugation. Antibiotic use has been well-established driver emergence and spread AMR. However, impact commonly used non-antibiotic compounds environmental pollutants largely overlooked. Recent studies found common prescription over-the-counter drugs, artificial sweeteners, food preservatives, pollutants, can increase conjugative plasmids. The potential mechanisms these promote plasmid transmission include increased membrane permeability, upregulation genes, formation reactive oxygen species, SOS response induction. Many questions remain around most conjugation clinical isolates long-term dissemination. By elucidating routinely pharmaceuticals, additives, AMR, action be taken to mitigate their closely monitoring disposal. This review will discuss recent progress understanding influence transmission, they transfer, level risk pose.

Language: Английский

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Zinc effects on bacteria: insights from Escherichia coli by multi-omics approach

mSystems, Journal Year: 2023, Volume and Issue: 8(6)

Published: Oct. 31, 2023

A long-term exposure of bacteria to zinc oxide and nanoparticles leads major alterations in bacterial morphology physiology. These included biochemical physiological processes promoting the emergence strains with multi-drug resistance virulence traits. After removal pressure, phenotype reversed back original state; however, certain changes at genomic, transcriptomic, proteomic level remained. Why is this important? The extensive intensive use supplements animal feed effects intestinal microbiota livestock may negatively impact health animals people. Therefore, it crucial understand monitor on microorganisms order adequately assess prevent potential risks.

Language: Английский

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Antibiotic resistance evolution driven synergistically by antibiotics and typical organic pollutants in antibiotic production wastewater

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 483, P. 136543 - 136543

Published: Nov. 17, 2024

Language: Английский

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Phenotypic and genomic insights into mutant with high nattokinase-producing activity induced by carbon ion beam irradiation of Bacillus subtilis

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 271, P. 132398 - 132398

Published: May 15, 2024

Language: Английский

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Transcriptional and biochemical changes in mouse liver following exposure to a metal/drug cocktail. Attenuating effect of a selenium-enriched diet

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 191, P. 114845 - 114845

Published: June 28, 2024

Real-life pollution usually involves simultaneous co-exposure to different chemicals. Metals and drugs are frequently abundantly released into the environment, where they interact bioaccumulate. Few studies analyze potential interactions between metals pharmaceuticals in these mixtures, although their joint effects cannot be inferred from individual properties. We have previously demonstrated that mixture (PC) of Cd Hg, metalloid As diclofenac (DCF) flumequine (FLQ) impairs hepatic proteostasis. To gain a deeper vision how PC affects mouse liver homeostasis, we evaluated here exposure upon some biochemical morphometric parameters, on transcriptional profiles selected group genes. found caused oxidative damage exceeded antioxidant capacity cells. The excessive stress response resulted an overabundance reducing equivalents, which hindered metabolism transport metabolites, including cholesterol bile acids, organs. These processes been linked metabolic inflammatory disorders, cancer, neurodegenerative diseases. Therefore, our findings suggest unintended mixtures environmental pollutants may underlie etiology many human Fortunately, also diet enriched with selenium mitigated harmful this combination toxicants.

Language: Английский

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Graphene/MWCNT/copper-nanoparticle fabricated printed electrode for diclofenac detection in milk and drinking water: Electrochemical and in-silico analysis

Journal of Molecular Liquids, Journal Year: 2024, Volume and Issue: 411, P. 125750 - 125750

Published: Aug. 12, 2024

Language: Английский

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New insights into the antimicrobial action and protective therapeutic effect of tirapazamine towards Escherichia coli-infected mice

International Journal of Antimicrobial Agents, Journal Year: 2023, Volume and Issue: 62(3), P. 106923 - 106923

Published: July 9, 2023

Language: Английский

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