The major facilitator superfamily (MFS) of proteins constitutes a large group of related solute transporters found across all known living taxa of organisms. The transporters of the MFS contain an extremely diverse array of substrates, including ions, molecules of intermediary metabolism, and structurally different antimicrobial agents. First discovered over 30 years ago, the MFS represents an important collection of integral membrane transporters. Bacterial microorganisms expressing multidrug efflux pumps belonging to the MFS are considered serious pathogens, accounting for alarming morbidity and mortality numbers annually. This review article considers recent advances in the structure-function relationships, the transport mechanism, and modulation of MFS multidrug efflux pumps within the context of drug resistance mechanisms of bacterial pathogens of public health concerns.
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http://dx.doi.org/10.1016/j.crmicr.2024.100248 | DOI Listing |
Cells
December 2024
Radiotherapy Department, Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
Definitive chemoradiotherapy (CRT) is a cornerstone of treatment for locoregionally advanced head and neck cancer (HNC). Research is ongoing on how to improve the tumor response to treatment and limit normal tissue toxicity. A major limitation in that regard is the growing occurrence of intrinsic or acquired treatment resistance in advanced cases.
View Article and Find Full Text PDFAm J Pathol
January 2025
Programa de Pós-Graduação em Anatomia Patológica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; Instituto Estadual do Cérebro Paulo Niemeyer (IECPN), Rio de Janeiro, Brazil. Electronic address:
Drug resistance is a major challenge in cancer therapy, and the expression of efflux pumps such as P-glycoprotein (P-gp, ABCB1) often correlates with poor prognosis in various tumors, including glioblastoma (GB). Considering that different roles for these proteins have been established in the biology of various tumors, this study aimed to investigate the functions of P-gp in GB-derived cells by evaluating its survival, migratory, and apoptosis-regulating capabilities, as well as its potential as a liquid biopsy biomarker. P-gp expression was diminished via siRNA to determine its exact role in GB biology.
View Article and Find Full Text PDFWater Res
January 2025
School of Civil and Environmental Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address:
Chlorine, the most widely utilized disinfectant for drinking water globally, has recently been implicated in facilitating the spread of antibiotic resistance genes (ARGs), raising concerns about its underestimated environmental and ecological risks. However, given the current fragmented research focus and results, a comprehensive understanding of the potential mechanisms and influencing factors behind chlorination-promoted ARGs transmission in drinking water systems is crucial. This work is the first to systematically review the variations in abundance, transmission mechanisms, influencing factors, and mitigation strategies related to ARGs during the chlorination process.
View Article and Find Full Text PDFJ Exp Med
February 2025
Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, St. Louis, MO, USA.
Dysfunctional lymphatic drainage from the central nervous system (CNS) has been linked to neuroinflammatory and neurodegenerative disorders, but our understanding of the lymphatic contribution to CNS fluid autoregulation remains limited. Here, we studied forces that drive the outflow of the cerebrospinal fluid (CSF) into the deep and superficial cervical lymph nodes (dcLN and scLN) and tested how the blockade of lymphatic networks affects CNS fluid homeostasis. Outflow to the dcLN occurred spontaneously in the absence of lymphatic pumping and was coupled to intracranial pressure (ICP), whereas scLN drainage was driven by pumping.
View Article and Find Full Text PDFMicroorganisms
December 2024
Laboratorio de Inmunoquímica II, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, Delegación Miguel Hidalgo, Mexico City C.P. 11340, Mexico.
Tuberculosis (TB), caused by (), remains one of the leading infectious causes of death globally, with drug resistance presenting a significant challenge to control efforts. The interplay between type 2 diabetes mellitus (T2DM) and TB introduces additional complexity, as T2DM triples the risk of active TB and exacerbates drug resistance development. This review explores how T2DM-induced metabolic and immune dysregulation fosters the survival of , promoting persistence and the emergence of multidrug-resistant strains.
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