Double-Edged Nanobiotic Platform with Protean Functionality: Leveraging the Synergistic Antibacterial Activity of a Food-Grade Peptide to Mitigate Multidrug-Resistant Bacterial Pathogens

Abstract

While persistent efforts are being made to develop a novel arsenal against bacterial pathogens, the development of such materials remains a formidable challenge. One such strategy is to develop a multimodel antibacterial agent which will synergistically combat bacterial pathogens, including multidrug-resistant bacteria. Herein, we used pediocin, a class IIa bacteriocin, to decorate Ag° and developed a double-edged nanoplatform (Pd-SNPs) that inherits intrinsic properties of both antibacterial moieties, which engenders strikingly high antibacterial potency against a broad spectrum of bacterial pathogens including the ESKAPE category without displaying adverse cytotoxicity. The enhanced antimicrobial activity of Pd-SNPs is due to their higher affinity with the bacterial cell wall, which allows Pd-SNPs to penetrate the outer membrane, inducing membrane depolarization and the disruption of membrane integrity. Bioreporter assays revealed the upregulation of cpxP, degP, and sosX genes, triggering the burst of reactive oxygen species which eventually cause bacterial cell death. Pd-SNPs prevented biofilm formation, eradicated established biofilms, and inhibited persister cells. Pd-SNPs display unprecedented advantages because they are heat-resistant, retain antibacterial activity in human serum, and alleviate vancomycin intermediate Staphylococcus aureus (VISA) infection in the mouse model. In addition, Pd-SNPs wrapped in biodegradable nanofibers mitigated Listeria monocytogenes in cheese samples. Collectively, Pd-SNPs exhibited excellent biocompatibility and in vivo therapeutic potency without allowing foreseeable resistance acquisition by pathogens. These findings underscore new avenues for using a potent biocompatible nanobiotic platform to combat a wide range of bacterial pathogens.

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

“…DiSC3(5) fluorescent dye can be absorbed by polarized cells and gathered in the phospholipid bilayer accompanied by fluorescence self-quenching. Once the membrane potential is disturbed, the dyes are released from cells and give off strong fluorescence, providing a manner to measure bacterial membrane potential [ 54 , 55 , 56 ]. As exhibited in Figure 7 , after incubation with different concentrations of coumarin 11f , the fluorescence intensity presented a dose-dependent increase, indicating that PHCI 11f could obviously dissipate the membrane potential and lead to membrane depolarization.…”

Synthesis of CuO and PAA-Regulated Silver-Carried CuO Nanosheet Composites and Their Antibacterial Properties

“…Silver nanoparticles (Ag NPs), which are used as a common antibacterial material, have been extensively studied in the past several decades [8,9], for example, in inhibiting the growth of bacteria [10], antimicrobial activity endurance [11], and the lack of risk of resistance of bacteria [12]. Relevant experiments have demonstrated the antibacterial mechanism of silver, that is, silver ions can cause the denaturation of proteins in the cell membrane of bacteria [13][14][15], and when the Ag + enters into the bacterial cell, it quickly combines with DNA in the cell and prevents the replication of the DNA double-helix structure [16]. It is commonly known that there is an accepted view of nanomaterials in a biological context, that is the smaller the particle size of the nanomaterial, the larger its specific surface area, which, in turn, makes it more biologically active [17,18].…”