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Unlabelled: Crosslinking agents, such as psoralen and UVA radiation, can be effectively used as antimicrobials and for treating several dysplastic conditions in humans, including some cancers. Yet, both cancer cells and bacteria can become resistant to these compounds, making it important to understand how resistance develops. Recently, several mutants were isolated that developed high-levels of resistance to these compounds through upregulation of components of the AcrAB-TolC-efflux pump.
View Article and Find Full Text PDFPhenotypic Profiling of Tigecycline-resistant Klebsiella pneumoniae Strains Induced In vitro.
Curr Microbiol
December 2024
Medical School of Chinese PLA, Beijing, China.
Tigecycline is one of the last-resort treatment options for infections caused by carbapenem-resistant Klebsiella pneumoniae (KP). Unfortunately, tigecycline resistance is increasingly reported and causes an unprecedented public health crisis worldwide. Although studies on tigecycline resistance are expanding, the underlying mechanisms are not fully understood.
View Article and Find Full Text PDFTargeting MarA N-terminal domain dynamics to prevent DNA binding.
Protein Sci
January 2025
Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Efflux is one of the mechanisms employed by Gram-negative bacteria to become resistant to routinely used antibiotics. The inhibition of efflux by targeting their regulators is a promising strategy to re-sensitize bacterial pathogens to antibiotics. AcrAB-TolC is the main resistance-nodulation-division efflux pump in Enterobacteriaceae.
View Article and Find Full Text PDFEfflux pumps mediate changes to fundamental bacterial physiology via membrane potential.
mBio
October 2024
School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom.
Efflux pumps are well known to be an important mechanism for removing noxious substances such as antibiotics from bacteria. Given that many antibiotics function by accumulating inside bacteria, efflux pumps contribute to resistance. Efflux pump inactivation is a potential strategy to combat antimicrobial resistance, as bacteria would not be able to pump out antibiotics.
View Article and Find Full Text PDFStructures and Efflux Mechanisms of the AcrAB-TolC Pump.
Subcell Biochem
July 2024
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
The global emergence of multidrug resistance (MDR) in gram-negative bacteria has become a matter of worldwide concern. MDR in these pathogens is closely linked to the overexpression of certain efflux pumps, particularly the resistance-nodulation-cell division (RND) efflux pumps. Inhibition of these pumps presents an attractive and promising strategy to combat antibiotic resistance, as the efflux pump inhibitors can effectively restore the potency of existing antibiotics.
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