Phenothiazines have their primary effects on the plasma membrane of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources, energy providing enzymes such as ATPases, and genes that regulate and code for permeability aspects of the bacterium. The responses of multi-drug (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis to the neuroleptic phenothiazine thioridazine are reviewed. The information collated suggests that this phenothiazine has the potential to cure XDR and MDR tuberculosis infections, a potential that has been recently demonstrated by its ability to cure 10 patients who presented with XDR TB infections. The mechanism by which this phenothiazine produces the desired effects within the infected macrophage is also discussed.
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PLoS Comput Biol
January 2025
Department of Physics, University of Toronto, Toronto, Ontario, Canada.
Efflux pumps that transport antibacterial drugs out of bacterial cells have broad specificity, commonly leading to broad spectrum resistance and limiting treatment strategies for infections. It remains unclear how efflux pumps can maintain this broad spectrum specificity to diverse drug molecules while limiting the efflux of other cytoplasmic content. We have investigated the origins of this broad specificity using theoretical models informed by the experimentally determined structural and kinetic properties of efflux pumps.
View Article and Find Full Text PDFMicrob Pathog
January 2025
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:
Following a period of disuse owing to the emergence of multidrug-resistant Gram-negative bacteria, colistin has regained global attention as an antibiotic of last resort. The resurgence in its utilization has led to a concurrent increase in acquired resistance, presenting a significant challenge in clinical treatment. Predominantly, resistance mechanisms involve alterations in the lipid A component of the lipopolysaccharide (LPS) structure.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.
The global dissemination of pathotypes with multidrug-resistant (MDR) and hypervirulent traits poses a threat to public health. The situation in Armenia is unclear, and we performed a comprehensive characterisation of 48 clinical isolates of , collected from 2018 to 2024. The majority of the isolates (64.
View Article and Find Full Text PDFMicroorganisms
January 2025
State Key Laboratory of Microbial Technology and Institute of Microbial Technology, Shandong University, Qingdao 266237, China.
Phenolic compounds are industrially versatile chemicals that have been successfully produced in microbial cell factories. Unfortunately, most phenolic compounds are highly toxic to cells in specific cellular environments or above a particular concentration because they form a complex with iron and promote hydroxyl radical production in Fenton reactions, resulting in the ferroptosis of cells. Here, we demonstrated that overexpression of efflux pumps and porins, including porins LamB and OmpN, and efflux pumps EmrAB, MdtABC, and SrpB, can enhance phloroglucinol (PG) tolerance by inhibiting the generation of hydroxyl radicals.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by the enzymatic degradation of antibiotics, target site modification, altered membrane permeability, multidrug efflux pumps, and their ability to form biofilms. Also, the evolution of drug resistance in , which is mainly driven by mobile genetic elements, is reported, with particular reference to plasmid-associated resistance, resistance islands, and insertion sequences.
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