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Multidrug resistance (MDR) in bacteria is a major concern these days. One of the reasons is the mutation in efflux pump that prevents the retention of antibiotics and drugs in the bacterial cell. The current work is a step to overcome MDR in bacteria via inhibition of efflux pump and further photoinhibition by thiolated chitosan coated cobalt doped zinc oxide nanoparticles (Co-ZnO) in visible light. Co-ZnO were synthesized in a size range of 40-60 nm. Antibacterial activity of the Co-ZnO against methicillin resistant Staphylococcus aureus (MRSA) was found 100% at a concentration of 10 μg/ml upon activation in sunlight for 15 min. Interestingly, it was found that cobalt as a dopant was able to increase the photodynamic and photothermal activity of Co-ZnO, as in dark conditions, there was only 3-5% of inhibition at 10 μg/ml of nanoparticle concentration. Upon excitation in light, these nanoparticles were able to generate reactive oxygen species (ROS) with a quantum yield of 0.23 ± 0.034. The nanoparticles were also generating heat, Because of the magnetic nature, thus helping in more killing. Thiolated chitosan further helped in blocking the efflux pump of MRSA. The current nanoparticles were also found biocompatible on human red blood cells (LD = 214 μg/ml). These data suggest that the MRSA killing ability was facilitated through efflux inhibition and oxidative stress upon excitation in visible light hence, were in accordance with previous findings.
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http://dx.doi.org/10.1016/j.jphotobiol.2019.01.021 | DOI Listing |
Mol Pharm
September 2025
Division of Pharmaceutics and Pharmacology, College of Pharmacy; Center for RNA Nanotechnology and Nanomedicine; James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
Liver cancer, particularly hepatocellular carcinoma (HCC), poses significant treatment challenges due to chemoresistance and cancer recurrence. Similar to customs at the border, the liver detoxifies incoming chemicals via efflux pumps and overexpresses ATP-binding cassette (ABC) drug exporters, leading to chemoresistance. ABC contains a multihomosubunit structure and a revolving transport mechanism, actively effluxing drugs from cancer cells, thereby reducing intracellular drug accumulation and therapeutic efficacy.
View Article and Find Full Text PDFMicrobiol Spectr
September 2025
Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon.
In Gram-negative bacteria, resistance-nodulation-division (RND)-type efflux pumps, particularly AcrAB-TolC, play a critical role in mediating resistance to antimicrobial agents and toxic metabolites, contributing to multidrug resistance. is an entomopathogenic bacterium that has garnered significant interest due to its production of bioactive specialized metabolites with anti-inflammatory, antimicrobial, and scavenger deterrent properties. In previous work, we demonstrated that AcrAB confers self-resistance to stilbenes in TT01.
View Article and Find Full Text PDFmBio
September 2025
Flinders Accelerator for Microbiome Exploration, College of Science and Engineering, Flinders University, Adelaide, South Australia, Australia.
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) ESKAPE pathogens pose a significant global health threat due to their ability to evade antibiotics through intrinsic and acquired mechanisms. These bacteria, including , , , , , and species, evade antibiotics through intrinsic and adaptive mechanisms. Common strategies include capsule formation, biofilm, β-lactamase production, and efflux activity.
View Article and Find Full Text PDFJ 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 PDFBioorg 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.
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