Seven Klebsiella pneumoniae and four Klebsiella oxytoca clinical isolates with different levels of resistance to ciprofloxacin were studied. Mutations in the topoisomerase genes were found in almost all strains, but the contribution of a multidrug efflux system homologous to AcrAB in Escherichia coli was also observed. Overexpression of this efflux system was demonstrated by immunoblotting with antibodies against E. coli AcrA.
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http://dx.doi.org/10.1128/AAC.46.12.3984-3986.2002 | DOI Listing |
Bioorg Med Chem Lett
January 2025
Contineum Therapeutics, 3565 General Atomics Court, Suite 200, San Diego, CA 92121, United States.
Novel kappa opioid receptor (KOR) agonists that preferentially activate G-protein signaling versus β-arrestin-2 recruitment are described. Starting from a literature-reported phenol-containing diphenethylamine KOR agonist, structure-activity relationship (SAR) studies revealed replacement of the phenol with various non-hydroxylated bicyclic heteroaromatics led to tertiary diarylethylamines which retained KOR agonist activity and improved metabolic stability in human liver microsomes. Further optimizations produced compound 39, a potent activator of G-protein signaling (GTPγS EC = 14 nM, 83 % E) that did not elicit a β-arrestin-2 recruitment functional response (E < 10 %).
View Article and Find Full Text PDFNPJ Antimicrob Resist
January 2025
Department of Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Regulatory elements controlling gene expression fine-tune bacterial responses to environmental cues, including antimicrobials, to optimize survival. Acinetobacter baumannii, a pathogen notorious for antimicrobial resistance, relies on efficient efflux systems. Though the role of efflux systems in antibiotic expulsion are well recognized, the regulatory mechanisms controlling their expression remain understudied.
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 PDFJ Hazard Mater
January 2025
Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China. Electronic address:
Arsenic contamination of water sources, whether from natural or industrial origins, represents a significant risk to human health. However, its impact on waterborne pathogens remains understudied. This research explores the effects of arsenic exposure on the opportunistic pathogen Pseudomonas aeruginosa, a bacterium found in diverse environments.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000, Cyberjaya, Selangor, Malaysia.
As a promising candidate for tackling drug-resistant cancers, triptolide, a diterpenoid derived from the Chinese medicinal plant Tripterygium wilfordii, has been developed. This review summarizes potential antitumor activities, including the suppression of RNA polymerase II, the suppression of heat shock proteins (HSP70 and HSP90), and the blockade of NF-kB signalling. Triptolide is the first known compound to target cancer cells specifically but spare normal cells, and it has success in treating cancers that are difficult to treat, including pancreatic, breast, and lung cancers.
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