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Designing effective antimicrobial oligomers remains challenging. Here, molecular dynamics simulations were used to design cationic antibacterial oligomers, based on conformational characteristics. Prescreened oligomeric structures were then synthesized via photo-induced atom transfer radical polymerization. The antibacterial oligomers were found to target the peptidoglycan layer of Gram-positive, antibiotic-resistant S taphylococcus aureus. The recent rise of antibiotic resistance amongst Staphylococcus aureus (S. aureus) populations has made treating Staph-based infections a global medical challenge. Therapies that specifically target the peptidoglycan layer of S. aureus have emerged as new treatment avenues, towards which bacteria are less likely to develop resistance. While the majority of antibacterial polymers/oligomers have the ability to disrupt bacterial membranes, the design parameters for the enhanced disruption of peptidoglycan outer layer of Gram-positive bacteria remain unclear. Here, the design of oligomeric structures with favorable conformational characteristics for improved disruption of the peptidoglycan outer layer of Gram-positive bacteria is reported. Molecular dynamics simulations were employed to inform the structure design and composition of cationic oligomers displaying collapsed and expanded conformations. The most promising diblock and triblock cationic oligomers were synthesized by photo-induced atom transfer radical polymerization (photo ATRP). Following synthesis, the diblock and triblock oligomers displayed average antibacterial activity of ~99% and ~98% for S. aureus and methicillin-resistant S. aureus (MRSA), respectively, at the highest concentrations tested. Importantly, triblock oligomers with extended conformations showed significantly higher disruption of the peptidoglycan outer layer of S. aureus compared to diblock oligomers with more collapsed conformation, as evidenced by a number of characterization techniques including scanning electron, confocal and atomic force microscopy. This work provides new insight into the structure/property relationship of antibacterial materials and advances the design of functional materials for combating the rise of drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Nanostructured titanium substrates provide inherent antimicrobial activity against drug-resistant fungi and bacteria, mimicking structures on the surface of naturally antimicrobial organisms. The addition of silver nanoparticles onto the nanostructures provides a secondary chemical antimicrobial mechanism and increases the efficacy in the response for both microbial species via low concentrations of silver. [Display omitted] Titanium and its alloys are commonly used implant materials. Once inserted into the body, the interface of the biomaterials is the most likely site for the development of implant-associated infections. Imparting the titanium substrate with high-aspect-ratio nanostructures, which can be uniformly achieved using hydrothermal etching, enables a mechanical contact-killing (mechanoresponsive) mechanism of bacterial and fungal cells. Interaction between cells and the surface shows cellular inactivation via a physical mechanism meaning that careful engineering of the interface is needed to optimse the technology. This mechanism of action is only effective towards surface adsorbed microbes, thus any cells not directly in contact with the substrate will survive and limit the antimicrobial efficacy of the titanium nanostructures. Therefore, we propose that a dual-action mechanoresponsive and chemical–surface approach must be utilised to improve antimicrobial activity. The addition of antimicrobial silver nanoparticles will provide a secondary, chemical mechanism to escalate the microbial response in tandem with the physical puncture of the cells. Hydrothermal etching is used as a facile method to impart variant nanostrucutres on the titanium substrate to increase the antimicrobial response. Increasing concentrations (0.25 M, 0.50 M, 1.0 M, 2.0 M) of sodium hydroxide etching solution were used to provide differing degrees of nanostructured morphology on the surface after 3 h of heating at 150 °C. This produced titanium nanospikes, nanoblades, and nanowires, respectively, as a function of etchant concentration. These substrates then provided an interface for the deposition of silver nanoparticles via a reduction pathway. Methicillin-resistant Staphylococcous aureus (MRSA) and Candida auris (C. auris) were used as model bacteria and fungi, respectively, to test the effectiveness of the nanostructured titanium with and without silver nanoparticles, and the bio-interactions at the interface. The presence of nanostructure increased the bactericidal response of titanium against MRSA from ∼ 10 % on commercially pure titanium to a maximum of ∼ 60 % and increased the fungicidal response from ∼ 10 % to ∼ 70 % in C. auris. Introducing silver nanoparticles increased the microbiocidal response to ∼ 99 % towards both bacteria and fungi. Importantly, this study highlights that nanostructure alone is not sufficient to develop a highly antimicrobial titanium substrate. A dual-action, physical and chemical antimicrobial approach is better suited to produce highly effective antibacterial and antifungal surface technologies. [ABSTRACT FROM AUTHOR]

Nanostructured titanium substrates provide inherent antimicrobial activity against drug-resistant fungi and bacteria, mimicking structures on the surface of naturally antimicrobial organisms. The addition of silver nanoparticles onto the nanostructures provides a secondary chemical antimicrobial mechanism and increases the efficacy in the response for both microbial species via low concentrations of silver. [Display omitted] Titanium and its alloys are commonly used implant materials. Once inserted into the body, the interface of the biomaterials is the most likely site for the development of implant-associated infections. Imparting the titanium substrate with high-aspect-ratio nanostructures, which can be uniformly achieved using hydrothermal etching, enables a mechanical contact-killing (mechanoresponsive) mechanism of bacterial and fungal cells. Interaction between cells and the surface shows cellular inactivation via a physical mechanism meaning that careful engineering of the interface is needed to optimse the technology. This mechanism of action is only effective towards surface adsorbed microbes, thus any cells not directly in contact with the substrate will survive and limit the antimicrobial efficacy of the titanium nanostructures. Therefore, we propose that a dual-action mechanoresponsive and chemical–surface approach must be utilised to improve antimicrobial activity. The addition of antimicrobial silver nanoparticles will provide a secondary, chemical mechanism to escalate the microbial response in tandem with the physical puncture of the cells. Hydrothermal etching is used as a facile method to impart variant nanostrucutres on the titanium substrate to increase the antimicrobial response. Increasing concentrations (0.25 M, 0.50 M, 1.0 M, 2.0 M) of sodium hydroxide etching solution were used to provide differing degrees of nanostructured morphology on the surface after 3 h of heating at 150 °C. This produced titanium nanospikes, nanoblades, and nanowires, respectively, as a function of etchant concentration. These substrates then provided an interface for the deposition of silver nanoparticles via a reduction pathway. Methicillin-resistant Staphylococcous aureus (MRSA) and Candida auris (C. auris) were used as model bacteria and fungi, respectively, to test the effectiveness of the nanostructured titanium with and without silver nanoparticles, and the bio-interactions at the interface. The presence of nanostructure increased the bactericidal response of titanium against MRSA from ∼ 10 % on commercially pure titanium to a maximum of ∼ 60 % and increased the fungicidal response from ∼ 10 % to ∼ 70 % in C. auris. Introducing silver nanoparticles increased the microbiocidal response to ∼ 99 % towards both bacteria and fungi. Importantly, this study highlights that nanostructure alone is not sufficient to develop a highly antimicrobial titanium substrate. A dual-action, physical and chemical antimicrobial approach is better suited to produce highly effective antibacterial and antifungal surface technologies. [ABSTRACT FROM AUTHOR]