Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Unlabelled: The growing resistance of to azoles poses a significant challenge in treating invasive fungal infections. This study aimed to investigate the synergistic effect of berbamine hydrochloride (BBM) combined with azoles in treating and explore the role of efflux pump inhibition in this synergy. The efficacy of combining BBM with itraconazole (ITC), voriconazole (VOR), and posaconazole (POS) was tested against 69 . strains that had been identified using the M38-A3 broth microdilution method. quantitative reverse transcription PCR (RT-qPCR) was used to measure gene expression related to synergy, while flow cytometry was employed to assess mitochondrial reactive oxygen species (ROS) levels, and Rhodamine 6G exocytosis assays were performed to quantify efflux pump activity. BBM alone showed no significant antifungal activity. BBM combined with POS exhibited synergy against 66 strains (95.7%), while two clinical isolates (Af05/Af08) and one defective strain (Δ) showed no synergy. Synergy with ITC was observed in three strains (4.3%), but not with VOR. In the non-synergistic Af05 and Af08 strains, the expression of the gene was significantly lower compared to wild-type (WT) strains. ROS levels increased significantly in WT with POS and BBM combination therapy, but not in the defective strains. Glucose uptake was also reduced in the POS-BBM combination. BBM enhances azole sensitivity in primarily by inhibiting the -mediated efflux pump, supported by reduced Rhodamine 6G exocytosis and synergy loss in -deficient strains. ROS accumulation and metabolic disruption may further contribute to this synergy. Targeting efflux pumps with BBM provides a novel strategy to combat azole resistance.
Importance: The combination of berbamine hydrochloride and posaconazole effectively enhances azole sensitivity in by reducing efflux pump activity and increasing reactive oxygen species levels. The findings offer a promising strategy to combat azole resistance in invasive fungal infections.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054048 | PMC |
| http://dx.doi.org/10.1128/spectrum.03184-24 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nanotechnology-based approaches to tackle bacterial infections.
J Control Release
September 2025
Di.S.T.A.Bi.F., University of Campania "Luigi Vanvitelli", Caserta, Italy. Electronic address:
Bacterial infections have emerged as a critical global health concern. More specifically, antibiotic resistant infections, severely compromise the effectiveness of standard antimicrobial therapies and prompting the exploration of alternative strategies. Among these, nanocarriers (NCs) have gained considerable interest due to their ability to improve drug solubility, stability, and targeted delivery while minimizing off-target effects.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of 3,3-dimethyl-2,3,4,9-tetrahydro-1H-carbazole derivatives as AcrB inhibitors with potent antibiofilm effect for reversing bacterial multidrug resistance.
Bioorg Chem
September 2025
Department of Medicinal Chemistry, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, PR China. Electronic address:
A series of novel 3,3-dimethyl-2,3,4,9-tetrahydro-1H-carbazole derivatives were rationally designed, synthesized and evaluated for their biological activity as AcrB inhibitors. The compounds were assessed for their antibiotic potentiating effects, followed by evaluation of Nile Red efflux inhibition, and off-target effects including activity on the outer and inner bacterial membranes. Ten compounds potentiated antibiotic activity at sub-inhibitory concentrations, reducing the minimum inhibitory concentrations (MICs) of at least one of the tested antibiotics by at least 8-fold, with three derivatives (7c, 11g, and 11i) achieving 32-fold MIC reductions at 128 μg/mL.
View Article and Find Full Text PDFObjectives: (formerly ) is a leading cause of invasive candidiasis and rapidly develops antifungal drug resistance during treatment. An increasing number of clinical isolates shows reduced susceptibility to echinocandins and azoles, leaving amphotericin B (AMB) as a last therapeutic option. Resistance of to this drug is rare and its underlying mechanisms are still not fully understood.
View Article and Find Full Text PDFNovel mutations associated with clofazimine resistance in Mycobacterium intracellulare.
J Antimicrob Chemother
September 2025
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Cen
Background: Clofazimine is a promising repurposed drug for treating Mycobacterium avium-intracellulare complex pulmonary disease, but its resistance mechanisms in Mycobacterium intracellulare remain poorly understood.
Objective: This study aims to elucidate the resistance mechanisms of M. intracellulare to clofazimine.
18-Crown-6-ether Utilizes Distinct Allosteric Interactions to Uncouple Transport by the Multidrug Efflux Pump EmrE.
Biochemistry
September 2025
Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
The recent discovery that the model multidrug efflux pump from , EmrE, can perform multiple types of transport suggests that this may be a compelling target for therapeutic intervention. Initial studies have identified several small-molecule substrates capable of inducing transporter-dependent susceptibility rather than the well-known antibiotic resistance phenotype. However, many questions regarding the underlying mechanism and regulation of this transporter still remain.
View Article and Find Full Text PDF