Traditional antimicrobial antibiotics are increasingly suffering from the emergence of multidrug resistance among pathogenic microorganisms. The antibiotic era is threatened by the ruthless rise of resistance in bacterial infections. A significant role in these resistance profiles is attributed to multidrug efflux pumps. Hence, much effort is being directed towards developing new compounds to overcome this problem. During our screening program of efflux pumps inhibitors (EPI) produced by bioactive Moroccan Actinobacteria, 210 isolates were screened for their antibacterial activities against strains containing a system of efflux pump AcrAB-TolC, fully functional, and its mutant, inactivated due to the insertion of transposon Tn903 in AcrAB operon, using the method of agar disc diffusion. The results showed that 14 isolates were able to produce EPI as they were active against the wild type strain but not against the mutant in comparison with the synthetic inhibitor L-Phe-L-Arg-β-naphthylamide (PaβN). We focused on the highest EPI activity produced by four strains (Z332, Z35/G, Z385/b and 136). Taxonomic studies and the 16S rDNA sequence indicated that these strains belonged to the species. This work could contribute to the discovery of a new class of antibacterial agents that could expand the therapeutic arsenal.
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http://dx.doi.org/10.3390/biotech11030022 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
() infections are increasingly challenging due to their propensity to form biofilms and low outer membrane permeability, especially in chronically infected patients with thick mucus. exhibits multiple drug resistance mechanisms, making it one of the most significant global public health threats. In this study, we found that moxifloxacin (MXC) and antibacterial peptides (ε-poly-l-lysine, ε-PLL) exhibited a synergistic effect against multidrug-resistant (MDR-).
View Article and Find Full Text PDFExpert Opin Drug Metab Toxicol
January 2025
Institut de R&D Servier, Paris-Saclay, F-91190 Gif-sur-Yvette, France.
Introduction: Drug-mediated inhibition of bile salt efflux transporters may cause liver injury. In vitro prediction of drug effects toward canalicular and/or sinusoidal efflux of bile salts from human hepatocytes is therefore a major issue, which can be addressed using liver cell-based assays.
Area Covered: This review, based on a thorough literature search in the scientific databases PubMed and Web of Science, provides key information about hepatic transporters implicated in bile salt efflux, the human liver cell models available for investigating functional inhibition of bile salt efflux, the different methodologies used for this purpose, and the modes of expression of the results.
Structure
December 2024
Center for Microbiome Research of Med-X Institute, Department of Critical Care Medicine, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China; The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address:
Multidrug-resistant Acinetobacter baumannii has emerged as one of the most antibiotic-resistant bacterial pathogens associated with nosocomial infection, with its resistance highly depending on multiple multidrug efflux pumps. Here, we report the cryoelectron microscopy (cryo-EM) structure of Acinetobacter drug efflux G (AdeG), the inner membrane component of one of three important resistance-nodulation-cell division (RND) pump family members in A. baumannii, which is involved in drug resistance to chloramphenicol, trimethoprim, ciprofloxacin, and clindamycin.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Microbiology, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia.
The widespread use of disinfectants and antiseptics has led to the emergence of nosocomial pathogens that are less sensitive to these agents, which in combination with multidrug resistance (MDR) can pose a significant epidemiologic risk. We investigated the susceptibility of nosocomial , , , and to a 0.05% chlorhexidine (CHX) solution and a biocidal S7 composite solution based on CHX (0.
View Article and Find Full Text PDFInt J Pharm
January 2025
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address:
Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.
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