Use of adjuvants to improve antibiotic efficacy and reduce the burden of antimicrobial resistance DOI
Teresa Gil‐Gil, Pablo Laborda, José Luis Martínez

et al.

Expert Review of Anti-infective Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

The increase of antibiotic resistance, together with the absence novel antibiotics, makes mandatory introduction strategies to optimize use existing antibiotics. Among them, molecules that their activity looks promising.

Language: Английский

Targeting Acinetobacter baumannii resistance-nodulation-division efflux pump transcriptional regulators to combat antimicrobial resistance DOI Creative Commons
Ruwani L. Wimalasekara,

Dawn White,

Ayush Kumar

et al.

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 25, 2025

Regulatory elements controlling gene expression fine-tune bacterial responses to environmental cues, including antimicrobials, optimize survival. Acinetobacter baumannii, a pathogen notorious for antimicrobial resistance, relies on efficient efflux systems. Though the role of systems in antibiotic expulsion are well recognized, regulatory mechanisms their remain understudied. This review explores current understanding these regulators, aiming inspire strategies combat resistance and improve therapeutic outcomes.

Language: Английский

Citations

1

Defense mechanisms of Salmonella against antibiotics: a review DOI Creative Commons
Anuradha Jeewantha Punchihewage-Don,

Priyanka Nilmini Ranaweera,

Salina Parveen

et al.

Frontiers in Antibiotics, Journal Year: 2024, Volume and Issue: 3

Published: Sept. 17, 2024

Salmonella is a foodborne pathogenic bacterium that causes salmonellosis worldwide. Also, considered serious problem for food safety and public health. Several antimicrobial classes including aminoglycosides, tetracyclines, phenols, β-Lactams are used to treat infections. Antibiotics have been prescribed decades infections caused by bacteria in human animal healthcare. However, intensive use of antibiotics resulted antibiotic resistance (AR) among several . Furthermore, multi-drug (MDR) has increased dramatically. In addition MDR , extensively drug resistant (XDR) as well pan (PDR) were reported globally. Therefore, increasing AR becoming universal health crisis. developed many mechanisms ensure its survival against antimicrobials. The most prominent defense these include enzymatic inactivation, expelling drugs from the cell through efflux pumps, altering structure drugs, changing or protecting targets drugs. Additionally, formation biofilms plasmid-mediated enhancing various antibiotics, making it challenging pathogen both healthcare industry settings. This review focuses exclusively on providing detailed overview

Language: Английский

Citations

8

Challenges and Opportunities with Antibiotic Discovery and Exploratory Research DOI
Laura J. V. Piddock, Rohit Malpani,

Alan J. Hennessy

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(8), P. 2445 - 2447

Published: July 22, 2024

Discovery and exploratory research can identify new antibiotics biological targets. However, failure rates are high, funding is insufficient to solve the scientific challenges attract researchers antibacterial R&D. Novel methods, including artificial intelligence, have been applied early-stage research, but these yet deliver antibiotics. The Global Antibiotic Research & Development Partnership (GARDP) investing in discovery an R&D education outreach program. GARDP's efforts, application of novel methods global networks develop antibiotics, helping address antimicrobial resistance sustainably over long-term.

Language: Английский

Citations

4

Multidrug efflux pumps of Pseudomonas aeruginosa show selectivity for their natural substrates DOI Creative Commons

Léna Mazza,

Alexandre Bory,

Alexandre Lüscher

et al.

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

Published: Jan. 9, 2025

Antibiotic-resistant Gram-negative bacteria are an increasing threat to human health. Strategies restore antibiotic efficacy include targeting multidrug efflux pumps by competitive pump inhibitors. These could be derived from natural substrates of these systems. In this work, we aimed elucidate the clinically relevant Mex Pseudomonas aeruginosa untargeted metabolomic approach. We constructed a PA14 mutant, genetically deleted in major MexAB-OprM, MexCD-OprJ, MexXY-OprM, and MexEF-OprN expressed mutant each individually inducible promoter. Comparative analysis exo-metabolomes identified 210 features that were more abundant supernatant overexpressors compared pump-deficient mutant. Most specific, while only few shared among several pumps. by-products secondary metabolites as well signaling molecules. Supernatants also showed decreased accumulation fatty acids, including long chain homoserine lactone quorum sensing Our data suggests P. appear have dedicated roles extruding molecules, metabolic by-products, oxidized acids. findings represent interesting starting point for development

Language: Английский

Citations

0

Photothermal–Photocatalytic Ternary Heterostructure for Solar Light-Driven Highly Efficient Degradation of Antimicrobial Agents and Inactivation of Superbugs DOI

Kaelin Gates,

Shivangee Rai,

Olorunsola Praise Kolawole

et al.

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

A significant proportion of antimicrobial agents, such as different antibiotics discharged into the environment via human and animal waste, poses problems for ecological balance health. Moreover, widespread overuse misuse have led to antibiotic-resistant bacteria (superbugs), which is one biggest global health in 21st century. Since utilization solar energy, an abundant natural resource photocatalytic system, we report design a photothermal–photocatalytic dual-functional light absorber-based ternary heterostructure using plasmonic gold nanoparticle (AuNP)-anchored WO3 nanoplatelet (WO3 NPL)-decorated reduced graphene oxide (r-GO) (AuNP/WO3 NPL/r-GO), exhibits strong absorption between 400 900 nm regions has capability sunlight-driven 100% degradation doxycycline antibiotics. Herein, show that due excellent photothermal performance AuNP r-GO heterostructure, local temperature increased under 785 NIR irradiation, boosted reaction kinetics enhancing transfer "hot carriers" formation reactive oxygen species (ROS). Furthermore, experimental data indicate by integrating materials, sunlight can be used antibiotic after 80 min irradiation. demonstrate sunlight-based inactivation carbapenem-resistant Enterobacteriaceae Escherichia coli (CRE E. coli) methicillin-resistant Staphylococcus aureus (MRSA) superbugs just exposing them 60 min. This study sheds on construction photothermally assisted heterostructures high-efficiency superbugs.

Language: Английский

Citations

0

Enhancing the Antibacterial Activity of Ciprofloxacin Against Klebsiella pneumoniae by Inhibiting the AcrAB-TolC Efflux Pump System Using Phenylalanine-arginine β-Naphthylamide DOI Creative Commons
Zeena Raad Hussein, Abdulameer M. Ghareeb

Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), Journal Year: 2025, Volume and Issue: 8(1), P. 56 - 61

Published: Feb. 11, 2025

Background: Klebsiella pneumoniae shows varying degrees of resistance to antibiotic treatment; this arises from multiple mechanisms, including the increased expression multidrug (MDR) efflux pumps. An pump inhibitor (EPI) is required overcome challenge and restore effectiveness antibiotics against present MDR K. pneumoniae. Objective: To investigate synergistic effect EPI Phenylalanine-Arginine β-Naphthylamide (PaβN) Ciprofloxacin (CIP) on genes AcrAB-TolC, isolated CIP-resistant Methods: 50 isolates were collected five different hospitals in Baghdad, Iraq. The minimum inhibitory concentration (MIC) values determined for CIP PaßN combination using broth micro-dilution method conducted ten resistant CIP. Moreover, level AcrA, AcrB, TolC four selected measured quantitative real-time polymerase chain reaction (qRT-PCR). Results: showed that 40/50 (80%) multidrug-resistant, 54% MIC was reduced significantly 2–8-fold treated with PaβN compared CIP-treated group. gene levels varied among isolates, a slight decrease AcrAB-TolC some those alone. Conclusions: promising finding combinations between inhibitors eliminating bacteria.

Language: Английский

Citations

0

Understanding Compound Efflux from Gram-Negative Bacteria, a Final Frontier for Antibiotic Discovery DOI
Rebecca J. Ulrich,

Paul J. Hergenrother

Microbial Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Multidrug-resistant bacterial infections are a rising threat to human health and currently account for 1.3 million deaths annually. Notably, 70% of these due gram-negative pathogens, no new classes gram-negative-active antibiotics have been approved by the US Food Drug Administration in past 55 years. The challenges converting compounds with vitro biochemical activity whole cell antibacterial significant, as outer membrane promiscuous efflux pumps thwart potential most antibiotic candidates. Significant strides made toward understanding compound penetration accumulation bacteria, but remains major obstacle drug discovery. Recent advances machine learning (ML) algorithms increased accessibility code programs nonexpert suggest artificial intelligence could help address problem. Here, we discuss work cast vision how ML can be utilized from bacteria.

Language: Английский

Citations

0

Resistant and Emergent Pathogens in Food Products DOI
Tomás G. Villa, L. Feijoo-Siota, José Luis R. Rama

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 15 - 40

Published: Jan. 1, 2025

Language: Английский

Citations

0

Innovative perspectives on the discovery of small molecule antibiotics DOI Creative Commons
Silvia T. Cardona, A. S. M. Zisanur Rahman, Julieta Novomisky Nechcoff

et al.

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: March 13, 2025

Antibiotics are essential to modern medicine, but multidrug-resistant (MDR) bacterial infections threaten their efficacy. Resistance evolution shortens antibiotic lifespans, limiting investment returns and slowing new approvals. Consequently, the WHO defines four innovation criteria: chemical class, target, mode of action (MoA), lack cross-resistance. This review explores innovative discovery approaches, including AI-driven screening, metagenomics, target-based strategies, develop novel antibiotics that meet these criteria combat MDR infections.

Language: Английский

Citations

0

Global health perspectives on antibacterial drug discovery and the preclinical pipeline DOI
Ursula Theuretzbacher,

Ravindra P. Jumde,

Alan J. Hennessy

et al.

Nature Reviews Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Language: Английский

Citations

0