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Methicillin-resistant Staphylococcus aureus (MRSA) has led to serious infections, especially in hospitals and clinics, where treatment and prevention have become more difficult due to the formation of biofilms. Owing to biofilm-derived antibiotic tolerance, the currently available traditional antibiotics have failed to treat MRSA infections. Hence, there is a urgent need to develop novel antibiotics for treating life-threatening MRSA infections. Lugdunin (cyclic peptide-1), a nonribosomal cyclic peptide produced by Staphylococcus lugdunensis, exhibits potent antimicrobial activity against MRSA. Amazingly, cyclic peptide-1 and its analogues cyclic peptide-11 and cyclic peptide-14 have the ability to disperse mature MRSA biofilms and show anti-clinical MRSA activity, including MRSA persister cells. In addition, these three cyclic peptide compounds have non-toxicity, lower hemolytic activity and lack of resistance development. Our results indicate that cyclic peptide-1, cyclic peptide-11, and cyclic peptide-14 have great potential as new antimicrobial drug candidates for the treatment of clinical MRSA infections. [ABSTRACT FROM AUTHOR]

Drug repurposing is considered a promising strategy to fight antimicrobial resistance (AMR). Methotrexate (Mtx), a classical anticancer drug, could strongly inhibit bacterial dihydrofolate reductase (DHFR). However, its poor permeability into bacteria and potent human cytotoxicity make it unsuitable as an antibacterial. Herein, we reported the conjugation of Mtx with a siderophore to construct "Trojan horse" antibacterials. The most potent conjugate 8 with nanomolar minimum inhibitory concentration (MIC) values exhibited over 1.00×103‐fold improved activity against Gram‐positive Streptococcus pneumoniae (S. pneumoniae) and Gram‐negative Yersinia enterocolitica (Y. enterocolitica) compared with Mtx, while possessing 2.31×103‐fold reduced human cytotoxicity, resulting in 2.08×106‐fold improvements in the therapeutic index. This proof‐of‐principle study verifies that siderophore conjugation is an effective strategy for developing new antibacterials from anticancer drugs. [ABSTRACT FROM AUTHOR]

Drug repurposing is considered a promising strategy to fight antimicrobial resistance (AMR). Methotrexate (Mtx), a classical anticancer drug, could strongly inhibit bacterial dihydrofolate reductase (DHFR). However, its poor permeability into bacteria and potent human cytotoxicity make it unsuitable as an antibacterial. Herein, we reported the conjugation of Mtx with a siderophore to construct "Trojan horse" antibacterials. The most potent conjugate 8 with nanomolar minimum inhibitory concentration (MIC) values exhibited over 1.00×103‐fold improved activity against Gram‐positive Streptococcus pneumoniae (S. pneumoniae) and Gram‐negative Yersinia enterocolitica (Y. enterocolitica) compared with Mtx, while possessing 2.31×103‐fold reduced human cytotoxicity, resulting in 2.08×106‐fold improvements in the therapeutic index. This proof‐of‐principle study verifies that siderophore conjugation is an effective strategy for developing new antibacterials from anticancer drugs. [ABSTRACT FROM AUTHOR]

A rationally designed mannosylated amphiphilic pillar[5]arene (Man@AP5) self-assembles into supramolecular vesicles with encapsulated vancomycin (Man@AP5-Van), which target macrophages, respond to both acid and cathepsin B, and release vancomycin (Van) rapidly inside macrophages. Man@AP5-Van significantly increases the intracellular concentration of Van, enhancing its antibacterial efficacy against intracellular MRSA. [ABSTRACT FROM AUTHOR]

As an energy-efficient and eco-friendly technique, capacitive deionization (CDI) has shown great potential for uranium (U(VI)) capture recently. However, extracting U(VI) with high kinetics, capacity and selectivity remains a major challenge due to the current surface active sites-based material and co-existing ions in aqueous solution. Here we rationally designed a layered 2D/2D niobium phosphate/holey graphene (HGNbP) electrode material, and originally demonstrated its efficient U(VI) capture ability via an electro-adsorption and electrocatalytic reduction coupling process. The less-accumulative loose layered architecture, open polycrystalline construction of niobium phosphate with active phosphate sites, and rich in-plane nano-pores on conductive graphene nanosheets endowed HGNbP with fast charge/ion transport, high electroconductivity and superior pseudocapacitance, which enabled U(VI) ions first to be electro-adsorbed, then physico-chemical adsorbed, and finally electrocatalysis reduced/deposited onto electrode surface without the limitation of active sites under a low potential of 1.2 V. Based on these virtues, the HGNbP exhibited a fast adsorption kinetics, with a high removal rate of 99.9% within 30 min in 50 mg L−1 U(VI) solution, and a high adsorption capacity up to 1340 mg g−1 in 1000 mg L−1 U(VI) solution. Furthermore, the good recyclability and selectivity towards U(VI) were also realized. [Display omitted] • A layered 2D/2D sheet to sheet HGNbP electrode was rationally designed. • HGNbP exhibited a removal rate of 99.9% in 30 min and capacity up to 1340 mg g−1. • The mechanism involves electro-adsorption, electro-reduction and coordination. • The method is energy-efficient, eco-friendly, and applied a low potential of 1.2 V. [ABSTRACT FROM AUTHOR]