Enhancing the Efficacy of Chloramphenicol Therapy for Escherichia coli by Targeting the Secondary Resistome

Antibiotics, Journal Year: 2024, Volume and Issue: 13(1), P. 73 - 73

Published: Jan. 12, 2024

The increasing prevalence of antimicrobial resistance and the limited availability new agents have created an urgent need for approaches to combat these issues. One such approach involves reevaluating use old antibiotics ensure their appropriate usage maximize effectiveness, as older could help alleviate burden on newer agents. An example antibiotic is chloramphenicol (CHL), which rarely used due its hematological toxicity. In current study, we employed a previously published transposon mutant library in MG1655/pTF2::

Language: Английский

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Bactofencin A Displays a Delayed Killing Effect on a Clinical Strain of Staphylococcus aureus Which Is Greatly Accelerated in the Presence of Nisin

Antibiotics, Journal Year: 2025, Volume and Issue: 14(2), P. 184 - 184

Published: Feb. 11, 2025

Background/objectives: Bacteriocins can be considered a novel source of natural alternatives to antibiotics or chemical food additives with the potential fight against clinical and pathogens. A number have already been commercialised as preservatives, but they also treat drug-resistant pathogens play role in immune modulation. To achieve their full potential, an understanding mode action is required. Methods: Bactofencin nisin were purified homogeneity by reversed-phase HPLC effect on mastitis pathogen Staphylococcus aureus DPC5246 was assessed cell viability assays flow cytometry. Results: We report that bactofencin displays delayed inhibitory pathogen, DPC5246, suggesting unusual action. This characteristic clearly visible BHI plate media, where formation inhibition zones staphylococcal strain took 23 h compared 6 for well-characterised nisin. killing injury demonstrated using cytometry, damage evident 4 after bacteriocin addition. Treatment 2 μM resulted approximately 20-fold higher numbers injured 50-fold dead cells when untreated cells. Combining lantibiotic faster at lower concentrations. When combined equal ratio, combination exhibited 4-fold increase alone. These results demonstrate may very effective therapeutic applications pathogenic staphylococci.

Language: Английский

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In-feed bacitracin methylene disalicylate alters microbiota function and increases antibiotic resistance in a dose-dependent manner

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Antibiotics are commonly used in turkey production to prevent and treat infection which can improve animal growth efficiency, but the mechanism by antibiotics performance, resistance risks associated with antibiotic inclusion levels remain unclear, particularly production. Therefore, we investigated longitudinal effect of subtherapeutic therapeutic doses bacitracin methylene disalicylate (BMD) on genes, mobile genetic elements, metabolism genes analyzing cecal metagenome. The dose BMD increased a vast array resistant (ARGs), conjugation-related type IV secretion system transduction-related for length experiment (78 days), while smaller, transient was observed due dose. Estimated bacterial rate, estimated metagenome assembled genome sequence coverage, decreased after 7 days in-feed BMD, group over time. Tryptophan synthesis from chorismate dose-dependent manner between - 35. Overall, effects microbiota temporary those were longer lasting. This study shows that antimicrobial belonging multiple classes, elements (MGEs) administration. enrichment these risk feed additives. BMD’s tryptophan provides potential metabolic target developing non-antibiotic microbiome modulatory promoters Importance Antibiotic use agricultural animals remains hotly debated important topic human, animal, environmental health. responses an fed additive allowed at both doses, not well understood. highlights is stronger selective pressure than related horizontal gene transfer. indicates could select bacteria may pose human Additionally, this highlighted activity beneficially bacteria, therefore be concentration metabolites (especially related) cecum. indicate promoting suppress generally, rather allowing beneficial generate metabolites.

Language: Английский

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Presence, Pathogenicity, Antibiotic Resistance, and Virulence Factors of Escherichia coli: A Review

Bacteria, Journal Year: 2025, Volume and Issue: 4(1), P. 16 - 16

Published: March 11, 2025

Escherichia coli (E. coli) is a Gram-negative, commensal/pathogenic bacteria found in human intestines and the natural environment. Pathogenic E. known as extra-intestinal pathogenic (ExPEC) or intestinal (InPEC). InPEC strains are separated into six groups, enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), enteroaggregative (EAEC), enterohaemorrhagic (EHEC), diffusely adherent (DAEC), that have various virulence factors cause infection. Virulence refer to combination of distinctive accessory traits affect broad range cellular processes pathogens. There two important directly interact with cells diarrhoeal diseases within intestines: adhesion colonization exotoxins. crucial for overcome host’s immune system result antibiotic resistance. Antibiotics used combat symptoms duration infection by coli. However, misuse overuse antibiotics led global concern Currently, colistin last-resort drug fight caused this bacterium. Antibiotic resistance can be achieved main ways: horizontal gene transfer mutation different genes. The genetic basis developing occurs through four mechanisms: limiting uptake, modification target, inactivation drug, active efflux drug. These mechanisms use remove from bacterial cell prevent entering binding targets. This prevents drugs working effectively, acquire classified phylogenetic groups (A, B1, B2, D1, D2, E, clade I). It very versatile bacterium easily adapt environmental factors. present review gathered information about pathogenicity, antimicrobial resistance, phylogenetics aspects interconnected; thus, it will provide on tracking spread genes using how evolve. Understanding variation help monitoring controlling outbreaks novel treatment. increasing rate ability evolve rapidly, suggest in-depth research needed these areas.

Language: Английский

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Combating Antibiotic Resistance: Mechanisms, Multidrug-Resistant Pathogens, and Novel Therapeutic Approaches: An Updated Review

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 402 - 402

Published: March 12, 2025

The escalating global health crisis of antibiotic resistance, driven by the rapid emergence multidrug-resistant (MDR) bacterial pathogens, necessitates urgent and innovative countermeasures. This review comprehensively examines diverse mechanisms employed bacteria to evade action, including alterations in cell membrane permeability, efflux pump overexpression, biofilm formation, target site modifications, enzymatic degradation antibiotics. Specific focus is given transport systems such as ATP-binding cassette (ABC) transporters, resistance–nodulation–division (RND) pumps, major facilitator superfamily (MFS) multidrug toxic compound extrusion (MATE) systems, small resistance (SMR) families, proteobacterial antimicrobial (PACE) families. Additionally, explores burden MDR pathogens evaluates emerging therapeutic strategies, quorum quenching (QQ), probiotics, postbiotics, synbiotics, peptides (AMPs), stem applications, immunotherapy, antibacterial photodynamic therapy (aPDT), bacteriophage. Furthermore, this discusses novel agents, animal-venom-derived compounds nanobiotics, promising alternatives conventional interplay between clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated proteins (Cas) adaptive immunity analyzed, revealing opportunities for targeted genetic interventions. By synthesizing current advancements underscores necessity interdisciplinary collaboration among biomedical scientists, researchers, pharmaceutical industry drive development agents. Ultimately, comprehensive analysis provides a roadmap future research, emphasizing need sustainable cooperative approaches combat safeguard health.

Language: Английский

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Biocides as Drivers of Antibiotic Resistance: A Critical Review of Environmental Implications and Public Health Risks

Environmental Science and Ecotechnology, Journal Year: 2025, Volume and Issue: unknown, P. 100557 - 100557

Published: March 1, 2025

The widespread and indiscriminate use of biocides poses significant threats to global health, socioeconomic development, environmental sustainability by accelerating antibiotic resistance. Bacterial resistance development is highly complex influenced significantly factors. Increased biocide usage in households, agriculture, livestock farming, industrial settings, hospitals produces persistent chemical residues that pollute soil aquatic environments. Such contaminants contribute the selection proliferation resistant bacteria antimicrobial genes (ARGs), facilitating their dissemination among humans, animals, ecosystems. In this review, we conduct a critical assessment four issues pertaining topic. Specifically, (i) role exerting selective pressure within resistome, thereby promoting microbial populations contributing spread (ARGs); (ii) triggering transient phenotypic adaptations bacteria, including efflux pump overexpression, membrane alterations, reduced porin expression, which often result cross-resistance multiple antibiotics; (iii) capacity disrupt make genetic content accessible, releasing DNA into environment remains intact under certain conditions, horizontal gene transfer determinants; (iv) bacterial cells, enhancing interactions between biofilms environment, strengthening biofilm cohesion, inducing mechanisms, creating reservoirs for microorganisms ARG dissemination. Collectively, review highlights public health implications use, emphasizing an urgent need strategic interventions mitigate proliferation.

Language: Английский

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Unveiling the potential of a novel drug efflux pump inhibitor to combat multidrug resistance in ESKAPEE pathogens, with a focus on Acinetobacter baumannii

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107513 - 107513

Published: March 1, 2025

Language: Английский

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Gene Expression Evaluation of mexT and mexF Genes of Pseudomonas aeruginosa under Antibiotic Stress

Medical Journal of Babylon, Journal Year: 2025, Volume and Issue: 22(1), P. 282 - 288

Published: Jan. 1, 2025

Abstract Background: Pseudomonas aeruginosa is a major cause of mortality and morbidity in those with immunodeficiencies who have cystic fibrosis antibiotic resistance. Objectives: To investigate the role genes responsible for pump efflux antibiotics ( mexF mexT ) their relation to Materials Methods: A total 100 clinical swabs were collected from different hospitals Baghdad, Iraq. The identification bacterial isolates was confirmed using VITEK2 compact system 16s rRNA . Drug susceptibility tests performed by system. Conventional polymerase chain reaction (PCR) used detection isolates. Reverse transcription (RT)-PCR detect gene expression effect ceftazidime amikacin on five Results: results culture biochemical showed that 50 P eruginosa They resistant cefotaxime (71.43%), cefepime meropenem (65.71%), imipenem (62.86%), gentamicin norfloxacin (60%), ciprofloxacin (51.43%). result conventional PCR 20 (57.1%) positive, whereas 18 (51.4%) RT-PCR indicated all exhibited downregulation gene. Conclusion: There positive correlation between

Language: Английский

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Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 3, 2025

Klebsiella pneumoniae is the causative agent of a wide range antibiotic-resistant infections, including nosocomial pneumonia and neonatal sepsis. We investigate here mechanisms underlying innate immune recognition this pathogen by focusing on role endosomal Toll-like receptors (TLRs), which sense prokaryotic nucleic acids, in comparison with TLR4, recognizes cell-wall lipopolysaccharide component. Lack functional TLRs made mice more susceptible to pulmonary infection K. pneumoniae, association reduced production proinflammatory chemotactic cytokines neutrophil recruitment lung. This phenotype was as severe that TLR4-deficient only moderately milder than lacking TLR adaptor MyD88. Notably, macrophages at same time TLR7, 9 13 were defective those TLR9 their ability produce cytokines, suggesting for RNA sensing TLR7 recognition. Collectively, our results unveil presence an integrated system DNA cooperates TLR4 detection clearance pneumoniae. These data may be useful devise alternative therapeutic approaches aimed stimulating responses against strains.

Language: Английский

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Antimicrobial Resistance: Linking Molecular Mechanisms to Public Health Impact

SLAS DISCOVERY, Journal Year: 2025, Volume and Issue: unknown, P. 100232 - 100232

Published: April 1, 2025

Antimicrobial resistance (AMR) develops into a worldwide health emergency through genetic and biochemical adaptations which enable microorganisms to resist antimicrobial treatment. β-lactamases (blaNDM, blaKPC) efflux pumps (MexAB-OprM) working with mobile elements facilitate fast proliferation of multidrug-resistant (MDR) exttreme drug-resistant (XDR) phenotypes thus creating major concerns for healthcare systems community as well the agricultural sector. The review dissimilarly unifies molecular pathways public implications study epidemiological data monitoring approaches innovative therapeutic solutions. Previous studies separating their attention between genetics clinical outcomes have been combined our approach delivers an all-encompassing analysis AMR. report investigates mechanisms feature enzymatic degradation pump overexpression together target modification horizontal gene transfer because these factors represent important contributors present-day AMR developments. This effects on hospital environments where it affects pathogens including MRSA, carbapenem-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa. document explores modern management methods that comprise WHO GLASS surveillance three strategies such CRISPR-modified genome editing bacteriophage treatments along peptides artificial intelligence diagnostic tools. resolution needs complete scientific global operational alongside state-of-the-art approaches. Worldwide infection burden requires both enhanced prevention procedures next-generation reduce cases effectively.

Language: Английский

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