Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis, was the leading cause of mortality worldwide in 2019 due to a single infectious agent. The growing threat of strains of M. tuberculosis untreatable by modern antibiotic regimens only exacerbates this problem. In response to this continued public health emergency, research into methods of potentiating currently approved antimicrobial agents against resistant strains of M. tuberculosis is an urgent priority, and a key strategy in this regard is the design of mycobacterial efflux pump inhibitors (EPIs). This review summarises the current state of knowledge surrounding drug-related efflux pumps in M. tuberculosis and presents recent updates within the field of mycobacterial EPIs with a view to aiding the design of an effective adjunct therapy to overcome efflux-mediated resistance in TB.
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http://dx.doi.org/10.1016/j.tim.2021.05.001 | DOI Listing |
Int 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.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Institute of Medical Microbiology, Semmelweis University, 1089 Budapest, Hungary.
In this study, the mechanisms implicated in delafloxacin resistance in strains were investigated. Delafloxacin is a novel, broad-spectrum fluoroquinolone that has been approved for clinical application. In our study, 43 strains were assessed, antimicrobial susceptibility testing was performed via the broth microdilution method, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, and imipenem were determined.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Laboratory of Basic and Applied Bacteriology, Department of Microbiology, Center of Biological Sciences, Universidade Estadual de Londrina, Londrina 86057-970, Brazil.
Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rapid emergence of resistance, drug repositioning offers a promising alternative.
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