Call for next-generation drugs that remove the uptake barrier to combat antibiotic resistance

Drug Discovery Today, Год журнала: 2023, Номер 28(10), С. 103753 - 103753

Опубликована: Авг. 26, 2023

Язык: Английский

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Photothermal responsive porous hollow microneedles as Chinese medicine versatile delivery system for wound healing

Smart Medicine, Год журнала: 2024, Номер 3(3)

Опубликована: Июль 1, 2024

Chinese medicine is identified as a candidate for wound healing. Attempts in this field tend to develop efficient dosage forms delivering with low side effects. In paper, we proposed novel photothermal responsive porous hollow microneedles (PRPH-MNs) versatile delivery system antibacterial treatment. The PRPH-MNs are composed of resin shells good mechanical property, hydrogel cores, and graphene oxide hybrid substrate. structure provides sufficient space loading the drug dispersed hydrogel, while could not only block direct contact between drugs sites but also provide channels facilitating release from core. addition, benefiting effect their substrate, be heated under near-infrared (NIR) irradiation controllable promotion release. Based on these features, have proved that Rhein loaded were effective promoting healing due property on-demand Thus, believe valuable different clinical applications.

Язык: Английский

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In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(3)

Опубликована: Янв. 8, 2024

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same strain is associated poor clinical outcomes high healthcare costs. The role persister cells, which sub-populations bacteria that survive for prolonged periods in presence bactericidal antibiotics, unclear. Using a cohort patients relapsed GNB-BSI, we aimed to determine how pathogen evolves within patient between initial subsequent episodes these changes impact persistence. Escherichia coli isolate pairs (initial isolates) from found 4/11 (36%) isolates displayed significant increase persisters cells relative infection isolate. In E. greatest (100-fold isolate), determined was due loss-of-function mutation ptsI gene encoding Enzyme I phosphoenolpyruvate phosphotransferase system. mutant equally virulent murine bacteremia model but exhibited 10-fold increased survival treatment. This work addresses controversy regarding relevance formation by providing compelling data not only do high-persister mutations arise during humans also mutants display challenge vivo.

Язык: Английский

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The potential new microbial hazard monitoring tool in food safety: Integration of metabolomics and artificial intelligence

Trends in Food Science & Technology, Год журнала: 2024, Номер 149, С. 104555 - 104555

Опубликована: Май 23, 2024

Язык: Английский

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Inosine monophosphate overcomes the coexisting resistance of mcr-1 and blaNDM-1 in Escherichia coli

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update

British Journal of Biomedical Science, Год журнала: 2024, Номер 81

Опубликована: Авг. 7, 2024

The global issue of antimicrobial resistance poses significant challenges to public health. World Health Organization (WHO) has highlighted it as a major health threat, causing an estimated 700,000 deaths worldwide. Understanding the multifaceted nature antibiotic is crucial for developing effective strategies. Several physiological and biochemical mechanisms are involved in development resistance. Bacterial cells may escape bactericidal actions drugs by entering physiologically dormant state known bacterial persistence. Recent findings this field suggest that persistence can be one main sources chronic infections. tolerance developed persister could tolerate high levels antibiotics give rise offspring. These offspring attributed mechanisms, especially This review attempts shed light on persister-induced current therapeutic

Язык: Английский

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Sub-inhibitory antibiotic treatment selects for enhanced metabolic efficiency

Microbiology Spectrum, Год журнала: 2024, Номер 12(2)

Опубликована: Янв. 16, 2024

ABSTRACT Bacterial growth and metabolic rates are often closely related. However, under antibiotic selection, a paradox in this relationship arises: efficacy decreases when bacteria metabolically dormant, yet antibiotics select for resistant cells that grow fastest during treatment. That is, selection counterintuitively favors with fast but slow metabolism. Despite apparent contradiction, have historically been characterized primarily the context of growth, whereas extent analogous changes metabolism is comparatively unknown. Here, we observed previously evolved antibiotic-resistant strains exhibited unique between whereby nutrient utilization became more efficient, regardless rate. To better understand unexpected phenomenon, used simplified model to simulate bacterial populations adapting sub-inhibitory through successive bottlenecking events. Simulations predicted bactericidal concentrations could enhanced efficiency, defined based on utilization: drug-adapted able achieve same biomass while utilizing less substrate, even absence Moreover, simulations restoring efficiency would re-sensitize exhibiting metabolic-dependent resistance; confirmed result using adaptive laboratory evolutions Escherichia coli carbenicillin Overall, these results indicate direct selective pressure treatment differences evolutionary may determine both different corresponding re-sensitization approaches. IMPORTANCE The sustained emergence pathogens combined stalled drug discovery pipelines highlights critical need underlying evolution mechanisms resistance. end, related, exclusively growth. favor Through an integrated approach mathematical modeling experiments, study thereby addresses significant knowledge gap whether drives complement, and/or act independently, resistance phenotypes.

Язык: Английский

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ZnFe Layered Double Hydroxide Nanosheets Loaded with Cu Single‐Atom Nanozymes with Multi‐Enzyme‐Like Catalytic Activities as an Effective Treatment for Bacterial Keratitis

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Bacterial keratitis (BK) is a type of corneal inflammation resulting from bacterial infection in the eye. Although nanozymes have been explored as promising materials wound healing, currently available lack sufficient catalytic activity and ability to penetrate biofilms, limiting their efficacy against treatment BK. To remedy this, ZnFe layered double hydroxide (ZnFe‐LDH) nanosheets are loaded with Cu single‐atom (Cu‐SAzymes) aminated dextran (Dex‐NH 2 ), formation nanozyme DT‐ZnFe‐LDH@Cu, which possesses peroxidase (POD)‐, oxidase (OXD)‐, catalase (CAT)‐like activities. This enables generate reactive oxygen species (ROS), such hydroxyl radicals ( • OH), superoxide anion radical (O •− singlet 1 O ) hydrogen peroxide (H thereby killing bacteria causing infections. The surface Dex‐NH enabled DT‐ZnFe‐LDH@Cu biofilm adsorb onto extracellular polymeric substances (EPS) produced by biofilm. Additionally, successfully repaired P. aeruginosa ‐infected injury BK rabbit model more effectively than commercially tobramycin eye drops. was enabled, part, reduce promoting polarization pro‐inflammatory macrophages (M1) anti‐inflammatory (M2) decrease expression α‐smooth muscle actin (α‐SMA) promote healing without scar formation. study provides an innovative concept for holds great scientific value clinical application potential.

Язык: Английский

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Fructose-enabled killing of antibiotic-resistant Salmonella enteritidis by gentamicin: Insight from reprogramming metabolomics

International Journal of Antimicrobial Agents, Год журнала: 2023, Номер 62(3), С. 106907 - 106907

Опубликована: Июнь 28, 2023

Salmonella enterica is a food-borne pathogen that poses severe threat to both poultry production and human health. Antibiotics are critical for the initial treatment of bacterial infections. However, overuse misuse antibiotics results in rapid evolution antibiotic-resistant bacteria, discovery development new declining. Therefore, understanding antibiotic resistance mechanisms developing novel control measures essential. In present study, GC-MS-based metabolomics analysis was performed determine metabolic profile gentamicin sensitive (SE-S) resistant (SE-R) S. enterica. Fructose identified as crucial biomarker. Further demonstrated global depressed central carbon metabolism energy SE-R. The decrease pyruvate cycle reduces NADH ATP, causing membrane potential, which contributes resistance. Exogenous fructose potentiated effectiveness killing SE-R by promoting cycle, NADH, ATP thereby increasing intake. Further, plus improved survival rate chicken infected with gentamicin-resistant vivo. Given metabolite structures conserved across species, from bacteria could be used biomarker breeding disease-resistant phenotypes chicken. strategy proposed fighting against enterica, including exploring molecules suppressed providing approach find targets disease breeding.

Язык: Английский

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L-Serine enables reducing the virulence of Acinetobacter baumannii and modulating the SIRT1 pathway to eliminate the pathogen

Microbiology Spectrum, Год журнала: 2024, Номер 12(3)

Опубликована: Янв. 19, 2024

ABSTRACT The emergence of high-virulent Acinetobacter baumannii strains increases the mortality patients and seriously affects their prognosis, which motivates us to explore novel ways control such infections. In this study, gas chromatography–mass spectrometry was adopted metabolic difference between high- low-virulent A. strains, decreased L-serine levels were identified as most crucial biomarker in strains. vitro , reduced virulence Beas 2B cells inhibited activation NLRP3 inflammasome via decreasing generation ROS mtROS release inflammatory cytokines (IL-18 IL-1β) through upregulating SIRT1. vivo Galleria mellonella model adopted. downregulated genes ( ompA carO omp 33-36), G. blacking speed well degree after infection. Taken together, we found that can reduce enhance host’s defense against pathogen, providing a strategy for treatment infections caused by . IMPORTANCE has become one common severe opportunistic pathogens hospitals. pose great threat increase risk nosocomial However, mechanism is still not understood. present potential biomarkers Our analysis revealed effect on reducing A.baumannii This discovery suggests targeting could be promising or adjunctive development treatments may provide substitute increasingly failed traditional antibacterial treatment.

Язык: Английский

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