The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)50/MIC90 values for AMXT-1501 in the range of 3.13–12.5 μM (2.24–8.93 μg /mL), including for methicillin-resistant Staphylococcus aureus (MRSA), CR Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of S. aureus and Enterococcus faecalis. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.
Background Polyphenols, as the predominant natural antioxidants in fruits, are key indicators of nutritional value. However, conventional polyphenol assays involve complex pretreatment and rely on their reducing properties, making them susceptible to interference and limiting sensitivity. Therefore, it is crucial to develop a simple and sensitive method for polyphenols detection. Results Herein, core-shell metal-organic framework nanomaterials (AuNR/PATP@ZIF-8) were constructed by in situ growth of zeolitic imidazolate framework-8 (ZIF-8) on gold nanorods/p-aminothiophenol (AuNRs/PATP). Surface-Enhanced Raman Scattering (SERS) was obtained utilizing the enrichment effect of ZIF-8 on small molecules and the chemical enhancement effect of ZIF-8 on gold nanorods (AuNRs). The polyphenols were sensitively detected based on the coordination of polyphenols with Zn 2+ using SERS. Gallic acid (GA), tannic acid (TA) and piceatannol (PIC) were detected as model polyphenols. The limit of detection (LOD) of GA, TA and PIC were 0.69 nM, 0.48 nM and 0.64 nM, and their linear ranges were 1 × 10 −9 - 2 × 10 −6 M, 1 × 10 −9 - 2 × 10 −6 M and 1 × 10 −9 - 1 × 10 −5 M, respectively, which was better than most of the previously reported works. Moreover, the method showed good reproducibility, stability and selectivity and was successfully applied to the evaluation of total polyphenols in grapes. Significance This method enables highly sensitive detection of polyphenols without complex pretreatment. This method was applied to the detection of total polyphenols in grapes with a wider linear range and higher sensitivity than that of the traditional folin-ciocalteu (F–C) detection, which has great potential in the trace detection of total polyphenols in fruits.