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Antimicrobial resistance is an issue of global relevance for the treatment of chronic wound infections. In this study, nano-in-micro hydrogels (microbeads) of chitosan and κ-carrageenan (CCMBs) containing curcumin-loaded rhamnosomes (Cur-R) were developed. The potential of Cur-R-CCMBs for improving the antibacterial activity and sustained release of curcumin was evaluated. Curcumin-loaded rhamnosomes (rhamnolipids functionalized liposomes) had a mean particle size of 116 ± 7 nm and a surface-charge of -24.5 ± 9.4 mV. The encapsulation efficiency of curcumin increased from 42.83 % ± 0.69 % in Cur-R to 95.24 % ± 3.61 % respectively after their embedding in CCMBs. SEM revealed smooth surface morphology of Cur-R-CCMBs. FTIR spectroscopy confirmed the presence of weak electrostatic and hydrophobic interactions among curcumin, rhamnosomes, and microbeads. Cur-R-CCMBs had demonstrated significant antibacterial activity against multi-drug resistant chronic wound pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. Cur-R-CCMBs also exhibited significantly higher anti-oxidant (76.85 % ± 2.12 %) and anti-inflammatory activity (91.94 % ± 0.41 %) as well as hemocompatibility (4.024 % ± 0.59 %) as compared to pristine microbeads. In vivo infection model of mice revealed significant reduction in the viable bacterial count of S. aureus (∼2.5 log CFU/mL) and P. aeruginosa (∼2 log CFU/mL) for Cur-R-CCMBs after 5 days. Therefore, nano-in-micro hydrogels can improve the overall efficacy of hydrophobic antimicrobials to develop effective alternative-therapeutics against resistant-pathogens associated with chronic wound infections.

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Biomaterial-associated infection (BAI) is considered a unique infection due to the presence of a biomaterial yielding frustrated immune-cells, ineffective in clearing local micro-organisms. The involvement of surface-adherent/surface-adapted micro-organisms in BAI, logically points to biomaterial surface-modifications for BAI-control. Biomaterial surface-modification is most suitable for prevention before adhering bacteria have grown into a mature biofilm, while BAI-treatment is virtually impossible through surface-modification. Hundreds of different surface-modifications have been proposed for BAI-control but few have passed clinical trials due to the statistical near-impossibility of benefit-demonstration. Yet, no biomaterial surface-modification forwarded, is clinically embraced. Collectively, this leads us to conclude that surface-modification is a dead-end road. Accepting that BAI is, like most human infections, due to surface-adherent biofilms (though not always to a foreign material), and regarding BAI as a common infection, opens a more-generally-applicable and therewith easier-to-validate road. Pre-clinical models have shown that stimuli-responsive nano-antimicrobials and antibiotic-loaded nanocarriers exhibit prolonged blood-circulation times and can respond to a biofilm's micro-environment to penetrate and accumulate within biofilms, prompt ROS-generation and synergistic killing with antibiotics of antibiotic-resistant pathogens without inducing further antimicrobial-resistance. Moreover, they can boost frustrated immune-cells around a biomaterial reducing the importance of this unique BAI-feature. Time to start exploring the nano-road for BAI-control.

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Planktonic bacterial presence in many industrial and environmental applications and personal health-care products is generally countered using antimicrobials. However, antimicrobial chemicals present an environmental threat, while emerging resistance reduces their efficacy. Suspended bacteria have no defense against mechanical attack. Therefore, we synthesized silica hexapods on an α-Fe2O3 core that can be magnetically-rotated to inflict lethal cell-wall-damage to planktonic Gram-negative and Gram-positive bacteria. Hexapods possessed 600 nm long nano-spikes, composed of SiO2, as shown by FTIR and XPS. Fluorescence staining revealed cell wall damage caused by rotating hexapods. This damage was accompanied by DNA/protein release and bacterial death that increased with increasing rotational frequency up to 500 rpm. Lethal puncturing was more extensive on Gram-negative bacteria than on Gram-positive bacteria, which have a thicker peptidoglycan layer with a higher Young's modulus. Simulations confirmed that cell-wall-puncturing occurs at lower nano-spike penetration levels in the cell walls of Gram-negative bacteria. This approach offers a new way to kill bacteria in suspension, not based on antimicrobial chemicals.

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In 2019, the new coronavirus disease (COVID-19), related to the severe acute respiratory syndrome coronavirus (SARS-CoV-2), started spreading around the word, giving rise to the world pandemic we are still facing. Since then, many strategies for the prevention and control of COVID-19 have been studied and implemented. In addition to pharmacological treatments and vaccines, it is mandatory to ensure the cleaning and disinfection of the skin and inanimate surfaces, especially in those contexts where the contagion could spread quickly, such as hospitals and clinical laboratories, schools, transport, and public places in general. Here, we report the efficacy of ZnO nanoparticles (ZnONPs) against SARS-CoV-2. NPs were produced using an ecofriendly method and fully characterized; their antiviral activity was tested in vitro against SARS-CoV-2, showing a decrease in viral load between 70% and 90%, as a function of the material's composition. Application of these nano-antimicrobials as coatings for commonly touched surfaces is envisaged.

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The rapid emergence of multidrug-resistant bacterial strains highlights the need for the development of new antimicrobial compounds/materials to address associated healthcare challenges. Meanwhile, the adverse side effects of conventional antibiotics on human health urge the development of new natural product-based antimicrobials to minimize the side effects. In this respect, we concisely review the recent scientific contributions to develop natural product-based nano-antibiotics. The focus of the review is on the use of flavonoids, peptides, and cationic biopolymer functionalized metal/metal oxide nanoparticles as efficient tools to hit the MDR bacterial strains. It summarizes the most recent aspects of the functionalized nanoparticles against various pathogenic bacterial strains for their minimal inhibitory concentrations and mechanism of action at the cellular and molecular levels. In the end, the future perspectives to materialize the in vivo applications of nano-antimicrobials are suggested based on the available research.

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The side effects and potential impacts on human health by traditional chemical additives as food preservatives (i.e., potassium and sodium salts) are the reasons why novel policies are encouraged by worldwide public health institutes. More natural alternatives with high antimicrobial efficacy to extend shelf life without impairing the cheese physicochemical and sensory quality are encouraged. This study is a comprehensive review of emerging preservative cheese methods, including natural antimicrobials (e.g., vegetable, animal, and protist kingdom origins) as a preservative to reduce microbial cheese contamination and to extend shelf life by several efforts such as manufacturing ingredients, the active ingredient for coating/packaging, and the combination of packaging materials or processing technologies. Essential oils (EO) or plant extracts rich in phenolic and terpenes, combined with packaging conditions and non-thermal methods, generally showed a robust microbial inhibition and prolonged shelf life. However, it impaired the cheese sensory quality. Alternatives including EO, polysaccharides, polypeptides, and enzymes as active ingredients/nano-antimicrobials for an edible film of coating/nano-bio packaging showed a potent and broad-spectrum antimicrobial action during shelf life, preserving cheese quality parameters such as pH, texture, color, and flavor. Future opportunities were identified in order to investigate the toxicological effects of the discussed natural antimicrobials' potential as cheese preservatives.

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The recent outbreaks of infectious diseases caused by multidrug-resistant pathogens have sounded a piercing alarm for the need of new effective antimicrobial agents to guard public health. Among different types of candidates, antimicrobial peptides (AMPs) and the synthetic mimics of AMPs (SMAMPs) have attracted significant enthusiasm in the past thirty years, due to their unique membrane-active antimicrobial mechanism and broad-spectrum antimicrobial activity. The extensive research has brought many drug candidates into clinical and pre-clinical development. Despite tremendous progresses have been made, several major challenges inherent to current design strategies have slowed down the clinical translational development of AMPs and SMAMPs. However, these challenges also triggered many efforts to redesign and repurpose AMPs. In this review, we will first give an overview on AMPs and their synthetic mimics, and then discuss the current status of their clinical translation. Finally, the recent advances in redesign and repurposing AMPs and SMAMPs are highlighted.

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Emerging antibiotic resistance in pathogens has posed considerable challenges to explore and examine the natural antimicrobials (NAMs). Due to the labile nature of NAMs, nano-delivery systems (NDS) are required to protect them from physiological degradation and allow controlled delivery to the targeted site of infection. In this study, corona modified NDS were developed using bovine serum albumin (BSA) on a chitosan core (CS) for sustained delivery of carvacrol (CAR), a natural antimicrobial agent, in the intestine. The optimal nano-formulations of the core (CS-NDS) and corona modified (BSA-CS-NDS) systems were fabricated with an average diameter of 52.4 ± 10.4 nm and 202.6 ± 6 nm, respectively. A shift in zeta-potential (ZP) from positive (+21 ± 3.6 mV) to negative values (-18 ± 2.6 mV) confirmed the electrostatic deposition of BSA corona on CS core. Under the influence of various simulated gastrointestinal conditions, BSA corona provided extra stability to NDS (ZP -38.5 mV), by ensuring delayed release and limited degradation in the gastric conditions. Mucoadhesive studies with quartz crystal microbalance with dissipation (QCM-D) revealed that BSA corona reduced the mucoadhesion of NDS at gastric pH, which enabled the effective delivery of CAR to the intestinal phase for successful eradication of Salmonella enterica.

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INTRODUCTION: Development of new antimicrobials with ever 'better' bacterial killing has long been considered the appropriate response to the growing threat of antimicrobial-resistant infections. However, the time-period between the introduction of a new antibiotic and the appearance of resistance amongst bacterial pathogens is getting shorter and shorter. This suggests that alternative pathways than making ever 'better' antimicrobials should be taken. AREAS COVERED: This review aims to answer the questions (1) whether we have means to circumvent existing antibiotic-resistance mechanisms, (2) whether we can revert existing antibiotic-resistance, (3) how we can prevent the development of antimicrobial-resistance against novel infection-control strategies, including nano-antimicrobials. EXPERT OPINION: Relying on relieving antibiotic-pressure and natural outcompeting of antimicrobial-resistant bacteria seems an uncertain way out of the antibiotic-crisis facing us. Novel, non-antibiotic, nanotechnology-based infection control-strategies are promising. At the same time, rapid development of new resistance mechanisms once novel strategies is taken into global clinical use, may not be ruled out and must be closely monitored. This suggests focusing research and development on designing suitable combinations of existing antibiotics with new nano-antimicrobials in a way that induction of new antimicrobial-resistance mechanisms is avoided. The latter suggestion, however, requires a change of focus in research and development.

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Silver nanoparticles (AgNPs) are well-known for their antimicrobial effects and several groups are proposing them as active agents to fight antimicrobial resistance. A wide variety of methods is available for nanoparticle synthesis, affording a broad spectrum of chemical and physical properties. In this work, we report on AgNPs produced by laser ablation synthesis in solution (LASiS), discussing the major features of this approach. Laser ablation synthesis is one of the best candidates, as compared to wet-chemical syntheses, for preparing Ag nano-antimicrobials. In fact, this method allows the preparation of stable Ag colloids in pure solvents without using either capping and stabilizing agents or reductants. LASiS produces AgNPs, which can be more suitable for medical and food-related applications where it is important to use non-toxic chemicals and materials for humans. In addition, laser ablation allows for achieving nanoparticles with different properties according to experimental laser parameters, thus influencing antibacterial mechanisms. However, the concentration obtained by laser-generated AgNP colloids is often low, and it is hard to implement them on an industrial scale. To obtain interesting concentrations for final applications, it is necessary to exploit high-energy lasers, which are quite expensive. In this review, we discuss the pros and cons of the use of laser ablation synthesis for the production of Ag antimicrobial colloids, taking into account applications in the food packaging field.

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Escherichia coli (E. coli) is one of the most important foodborne pathogens to the food industry responsible for diseases as bloody diarrhea, hemorrhagic colitis and life-threatening hemolytic-uremic syndrome. For controlling and eliminating E. coli, metal nano-antimicrobials (NAMs) are frequently used as bioactive systems for applications in food treatments. Most NAMs provide controlled release of metal ions, eventually slowing down or completely inhibiting the growth of undesired microorganisms. Nonetheless, their antimicrobial action is not totally unraveled and is strongly dependent on metal properties and environmental conditions. In this work, we propose the use of matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry as a powerful tool for direct, time efficient, plausible identification of the cell membrane damage in bacterial strains exposed to copper-based antimicrobial agents, such as soluble salts (chosen as simplified AM material) and copper nanoparticles. E. coli ATCC 25922 strain was selected as 'training bacterium' to set up some critical experimental parameters (i.e. cell concentration, selection of the MALDI matrix, optimal solvent composition, sample preparation method) for the MS analyses. The resulting procedure was then used to attain both protein and lipid fingerprints from E. coli after exposure to different loadings of Cu salts and NPs. Interestingly, bacteria exposed to copper showed over-expression of copper binding proteins and degradation of lipids when treated with soluble salt. These findings were completed with other investigations, such as microbiological experiments. Copyright © 2016 John Wiley & Sons, Ltd.

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