Chimeric Tobramycin-Based Adjuvant TOB-TOB-CIP Potentiates Fluoroquinolone and β-Lactam Antibiotics against Multidrug-Resistant Pseudomonas aeruginosa

ACS Infectious Diseases, Journal Year: 2023, Volume and Issue: 9(4), P. 864 - 885

Published: March 14, 2023

According to the World Health Organization, antibiotic resistance is a global health threat. Of particular importance are infections caused by multidrug-resistant Gram-negative bacteria including Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa for which limited treatment options exist. Multiple simultaneously occurring mechanisms outer membrane impermeability, overexpression of efflux pumps, antibiotic-modifying enzymes, modification genes targets have made drug development more difficult against these pathogens. One strategy cope with challenges use permeabilizers that increase intracellular concentration antibiotics when used in combination. In some circumstances, this approach can rescue from or repurpose currently marketed antibiotics. Tobramycin-based hybrid adjuvants combine two membrane-active components been previously shown potentiate facilitating transit through membrane, resulting increased accumulation within cell. Herein, we extended concept tobramycin-based chimeras engineering up three different warheads such as tobramycin, 1-(1-naphthylmethyl)-piperazine, ciprofloxacin, cyclam into central 1,3,5-triazine scaffold. Chimera 4 (TOB-TOB-CIP) consistently synergized levofloxacin, moxifloxacin wild-type fluoroquinolone-resistant P. aeruginosa. Moreover, susceptibility breakpoints ceftazidime, aztreonam, imipenem were reached using triple combination chimera ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam, respectively, β-lactamase-harboring Our findings demonstrate form novel class potentiators capable restoring activity

Language: Английский

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A Mini-Review of Anti-Listerial Compounds from Marine Actinobacteria (1990–2023)

Antibiotics, Journal Year: 2024, Volume and Issue: 13(4), P. 362 - 362

Published: April 15, 2024

Among the foodborne illnesses, listeriosis has third highest case mortality rate (20–30% or higher). Emerging drug-resistant strains of Listeria monocytogenes, a causative bacterium listeriosis, exacerbate seriousness this public health concern. Novel anti-Listerial compounds are therefore needed to combat challenge. In recent years, marine actinobacteria have come be regarded as promising source novel antimicrobials. Hence, our aim was provide narrative available literature and discuss trends regarding bioprospecting for new compounds. Four databases were searched review: Academic Search Ultimate, Google Scholar, ScienceDirect, South African Thesis Dissertations. The search restricted peer-reviewed full-text manuscripts that discussed antimicrobials written in English from 1990 December 2023. total, past three decades (1990–December 2023), only 23 been tested their potential. Out reported compounds, 2-allyoxyphenol, adipostatins E–G, 4-bromophenol, ansamycins (seco-geldanamycin B, 4.5-dihydro-17-O-demethylgeldanamycin, seco-geldanamycin) found possess activity. Thus, survey reveals scarcity published assays testing capacity bioactive sourced during period.

Language: Английский

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Structure and mechanism basis of β-lactam activity against Mycobacterium tuberculosis: A review of literature

Indian Journal of Tuberculosis, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Enhancing antibiotic therapy through comprehensive pharmacokinetic/pharmacodynamic principles

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 25, 2025

Antibiotic therapy relies on understanding both pharmacokinetics (PK) and pharmacodynamics (PD), which respectively address drug absorption, distribution, elimination, the relationship between concentration antimicrobial efficacy. This review synthesizes decades of research, drawing from in-vitro studies, in-vivo models, clinical observations, to elucidate temporal dynamics antibiotic activity. We explore how these dynamics, including concentration-effect relationships post effects, inform classification antibiotics based their PD profiles. Additionally, we discuss pivotal role PK/PD principles in determining optimal dosage regimens. By providing a comprehensive overview therapy, this aims enhance improve treatment outcomes practice.

Language: Английский

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Recent progress in synthetic strategies for novel β-lactams linked with five-membered heterocycles (N/O/S): advances in medicinal chemistry (2020–2025)

Medicinal Chemistry Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Language: Английский

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Extended-Spectrum Beta-Lactamases (ESBLs) Gene Mutations in Kuwait: How Much Do We Know? Not Much!

Bacteria, Journal Year: 2025, Volume and Issue: 4(2), P. 22 - 22

Published: April 30, 2025

Antibiotic resistance is a major problem worldwide, especially with the overuse and misuse of antibiotics. This makes it more challenging to treat patients infected antibiotic-resistant bacteria, costs on health system. review article describes extended-spectrum β-lactam antibiotics as most used antibacterial agents, how bacteria developed beta-lactamases (ESBLs) resist these The focuses ESBLs in Kuwait uncover which are present what ESBL gene mutations have been found this country. literature review, surprisingly, revealed limited number studies mutations, published over last 25 years. results showed that has an alarming bacterial strains mutations. These reported different isolated from types specimens, were collected hospitals Kuwait. data scattered not linked or analysed together highlight big picture highlights amount research up expectations country like Kuwait, high-standard facilities. Bearing mind geographic area relatively small, authors paper think there might be spreading need explored, collaboration needed among researchers address risky situation.

Language: Английский

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Natural detoxification of antibiotics in the environment: A one health perspective

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 24, 2022

The extended concept of one health integrates biological, geological, and chemical (bio-geo-chemical) components. Anthropogenic antibiotics are constantly increasingly released into the soil water environments. fate these drugs in thin Earth space (“critical zone”) where biosphere is placed determines effect antimicrobial agents on microbiosphere, which can potentially alter composition ecosystem lead to selection antibiotic-resistant microorganisms including animal human pathogens. However, environments highly heterogeneous their local composition; thus permanence activity antibiotics. This a case “molecular ecology”: antibiotic molecules adsorbed eventually inactivated by interacting with biotic abiotic that present at different concentrations places. There poorly explored aspects pharmacodynamics (PD, biological action) pharmacokinetics (PK, rates decay) In this review, we explore various factors contributing detoxification environment. These range from spontaneous degradation detoxifying effects produced clay minerals (forming geochemical platforms degradative reactions influenced light, metals, or pH), charcoal, natural organic matter (including cellulose chitin), biodegradation bacterial populations complex consortia “bacterial subsistence”; other words, microbes taking as nutrients), planktonic microalgae, fungi, plant removal degradation, sequestration living dead cells (necrobiome detoxification). Many processes occur particulated material bacteria origins (microbiota coalescence) might also attach (microbiotic particles), thereby determining environmental PK/PD influencing resistant bacteria. exploration field requires multidisciplinary effort developing molecular ecology antibiotics, but could result much more precise determination hazards production release.

Language: Английский

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A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

npj Antimicrobials and Resistance, Journal Year: 2023, Volume and Issue: 1(1)

Published: June 1, 2023

Abstract Syphilis, caused by the spirochete Treponema pallidum subsp. (hereafter called T. ), is re-emerging as a worldwide sexually transmitted infection. A single intramuscular dose of benzathine penicillin G preferred syphilis treatment option. Both supply shortage concerns and potential for acquired antibiotic resistance further need to broaden repertoire therapeutics. We reasoned that other β-lactams may be equally or more effective at targeting disease-causing agent, , but have yet discovered due previous lack continuous in vitro culture system. Recent technical advances with respect propagation allowed us conduct high-throughput screen almost 100 β-lactams. Using several molecular cellular approaches we developed adapted, identified confirmed efficacy were similar outperformed current standard, G. These options are either currently used treat bacterial infections synthetic derivatives naturally occurring compounds. Our studies not only additional therapeutics resolution syphilis, provide techniques study complex biology —a has plagued human health centuries.

Language: Английский

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Navigating Antibacterial Frontiers: Landscape Analysis of Antibiotics, Resistance Mechanisms and Emerging Therapeutic Strategies

Published: Jan. 10, 2024

Developing effective antibacterial solutions has become paramount in maintaining global health this era of increasing bacterial threats and rampant antibiotic resistance. Traditional antibiotics have played a significant role combating infections throughout history. However, the emergence novel resistant strains necessitates constant innovation research. We analyzed data on antibacterials from CAS Content CollectionTM, largest human-curated collection published scientific knowledge, proven valuable for quantitative analysis knowledge. Our focuses mining Collection recent publications (since 2012). This article aims to explore intricate landscape research while reviewing advancement traditional emerging strategies. By delving into resistance mechanisms, paper highlights need find alternate strategies address growing concern.

Language: Английский

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Novel Variant of New Delhi Metallo-Beta-Lactamase (blaNDM-60) Discovered in a Clinical Strain of Escherichia coli from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance

Antibiotics, Journal Year: 2024, Volume and Issue: 13(12), P. 1158 - 1158

Published: Dec. 2, 2024

Background/Objectives: Carbapenem resistance poses a significant health threat. This study reports the first detection and characterization of novel variant New Delhi metallo-β-lactamase (blaNDM-60) in Escherichia coli from United Arab Emirates (UAE), including its genetic context relationship to global strains. Methods: NDM-60-producing E. was isolated rectal swab during routine screening. Characterization involved whole-genome sequencing, antimicrobial susceptibility testing, comparative genomic analysis with 66 known NDM variants. Core genome performed against 42 strains, single other reported NDM-60-positive isolate. Results: The strain demonstrated extensive drug resistance, β-lactam/β-lactamase inhibitor combinations, notably taniborbactam. NDM-60 differs closely related NDM-5 by amino acid substitution (Asp202Asn) two substitutions (Val88Leu Met154Leu) compared NDM-1. is located on nonconjugative IncX3 plasmid. belongs sequence type 940 (ST940). Phylogenetic revealed high diversity among ST940 which carry plethora genes originated humans, animals, environment diverse geographic locations. Conclusions: emergence UAE represents evolution carbapenemase diversity. Its presence plasmid may limit spread; however, profile concerning. Further studies are needed determine prevalence, dissemination, clinical impact NDM-60. underscores ongoing challenge managing critical importance vigilant molecular surveillance. It also highlights pressing demand discover new antibiotics fight resistant bacteria.

Language: Английский

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