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Objectives: To investigate the potential synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii strains grown in planktonic phase or as biofilms.
Methods: Sixteen strains were investigated, including nine colistin-susceptible (MIC range 0.5-1 mg/L) and seven colistin-resistant (MIC range 16-256 mg/L) strains. Synergism of colistin in combination with N-acetylcysteine was investigated by chequerboard assays. The activity of colistin/N-acetylcysteine combinations was further evaluated by time-kill assays with planktonic cultures (three colistin-resistant strains and one colistin-susceptible strain) and by in vitro biofilm models (three colistin-resistant and three colistin-susceptible strains).
Results: Chequerboard assays revealed a relevant synergism of colistin/N-acetylcysteine combinations with all colistin-resistant strains, whereas no synergism was observed with colistin-susceptible strains. Time-kill assays showed a concentration-dependent potentiation of colistin activity by N-acetylcysteine against colistin-resistant strains, with eradication of the culture by combinations of N-acetylcysteine at 8000 mg/L plus colistin at 2 or 8 mg/L. A static effect during the first 8 h of incubation was demonstrated with the colistin-susceptible strain exposed to 0.25 × MIC colistin plus 8000 mg/L N-acetylcysteine. A remarkable antibiofilm synergistic activity of 8 mg/L colistin plus 8000 mg/L N-acetylcysteine was demonstrated with all colistin-resistant and colistin-susceptible strains. The effects were greater with colistin-resistant strains (marked reduction of viable biofilm cells was observed at sub-MIC colistin concentrations).
Conclusions: N-acetylcysteine, at concentrations achievable by topical administration, was shown to revert the colistin-resistant phenotype in A. baumannii, and to exert a relevant activity against biofilms of colistin-susceptible and colistin-resistant A. baumannii strains.
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http://dx.doi.org/10.1093/jac/dky185 | DOI Listing |
PLoS One
September 2025
Faculty of Health, Institute of Pharmacology and Toxicology, Centre for Biomedical Education and Research (ZBAF), School of Medicine, Witten/Herdecke University, Witten, Germany.
The emergence of antibiotic resistance continues to pose a significant global challenge. Drug repurposing, wherein existing therapeutics are evaluated for new applications, offers a promising strategy to address this issue. Farnesyltransferase inhibitors (FTIs), initially developed for cancer therapy, have demonstrated antimicrobial activity against several gram-positive bacteria.
View Article and Find Full Text PDFAntibiotics (Basel)
August 2025
Barcelona Institute for Global Health (ISGlobal), 08036 Barcelona, Spain.
: Infections caused by multidrug-resistant (MDR) are steadily increasing, thus the discovery and development of new and effective agents are needed. Antimicrobial peptides (AMPs) are a heterogeneous group of innate defense system peptides with broad antimicrobial activity. In this study, 17 AMPs were tested, identifying CAP-18, a cathelicidin-based compound, as the most active.
View Article and Find Full Text PDFAntibiotics (Basel)
August 2025
Public Health and Environmental Health Laboratory, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru.
Pigs and cattle have been implicated as reservoirs of antimicrobial resistance genes (ARGs) that can spread to humans, and houseflies are considered potential carriers of bacteria with ARGs that could contribute to their spread to the environment, including food, animals, and humans. In this study, 107, 145, and 127 strains were isolated from houseflies, pigs, and cattle, respectively, from a slaughterhouse in Lima, Peru. Antimicrobial susceptibility testing was performed using the Kirby-Bauer method, where thirteen antibiotics were used.
View Article and Find Full Text PDFMicrobiol Spectr
August 2025
Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha, PR China.
Multi-drug-resistant infections are becoming increasingly threatening, and the development of novel antimicrobial drugs is indispensable. Herein, we demonstrate that this novel peptide is highly active against colistin-resistant strain and shows sustained killing efficacy . Mechanistic studies showed that D-Q7 interacted with phosphatidylglycerol and lipopolysaccharide in the bacterial cell membrane, with an increase in intracellular ROS as well as a decrease in ATP level, ultimately leading to cell membrane disruption and bacterial death.
View Article and Find Full Text PDFMicrobiol Spectr
August 2025
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Colistin resistance in carbapenem-resistant (CRKP) poses a significant global health challenge, as colistin remains the last-resort antibiotic for treating multidrug-resistant infections. This study aimed to investigate the prevalence and molecular mechanisms underlying colistin resistance in CRKP (Col-CRKP) isolates in Henan, China, from 2021 to 2024. The minimum inhibitory concentrations of colistin for 134 .
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