The rapid dissemination of antibiotic resistance accelerates the desire for new antibacterial agents. Here, a class of antimicrobial peptides (AMPs) is designed by modifying the structural parameters of a natural chickpea-derived AMP-Leg2, termed "functionalized chickpea-derived Leg2 antimicrobial peptides" (FCLAPs). Among the FCLAPs, KTA and KTR show superior antibacterial efficacy against the foodborne pathogen Escherichia coli (E. coli) O157:H7 (with MICs in the range of 2.5-4.7 μmol L −1 ) and demonstrate satisfactory feasibility in alleviating E. coli O157:H7-induced intestinal infection. Additionally, the low cytotoxicity along with insusceptibility to antimicrobial resistance increases the potential of FCLAPs as appealing antimicrobials. Combining the multi-omics profiling andpeptide-membrane interaction assays, a unique dual-targeting mode of action is characterized. To specify the antibacterial mechanism, microscopical observations, membrane-related physicochemical properties studies, and mass spectrometry assays are further performed. Data indicate that KTA and KTR induce membrane damage by initially targeting the lipopolysaccharide (LPS), thus promoting the peptides to traverse the outer membrane. Subsequently, the peptides intercalate into the peptidoglycan (PGN) layer, blocking its synthesis, and causing a collapse of membrane structure. These findings altogether imply the great potential of KTA and KTR as promising antibacterial candidates in combating the growing threat of E. coli O157:H7.
The use of multiple-level non-uniform rectangular mesh in coupled flow and sediment transport modeling is preferred to achieve high accuracy in important region without increasing computational cost greatly. Here, a robust coupled hydrodynamic and non-equilibrium sediment transport model is developed on non-uniform rectangular mesh to simulate dam break flow over movable beds. The enhanced shallow water and sediment transport equations are adopted to consider the mass and momentum exchange between the flow phase and sediment phase. The flux at the interface is calculated by the positivity preserving central upwind scheme, which belongs to Godunov-type Riemann-problem-solver-free central schemes and is less expensive than other popular Riemann solvers while still capable of tracking wet/dry fronts accurately. The nonnegative water depth reconstruction method is used to achieve second-order accuracy in space. The model was first verified against two laboratory experiments of dam break flow over irregular fixed bed. Then the quantitative performance of the model was further investigated by comparing the computational results with measurement data of dam break flow over movable bed. The good agreements between the measurements and the numerical simulations are found for the flow depth, velocity and bed changes.
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