Nano-textured surfaces (NTS) are critical to organisms as self-adaptation and survival tools. These NTS have been actively mimicked in the process of developing bactericidal surfaces for diverse biomedical and hygiene applications. To design and fabricate bactericidal topographies effectively for various applications, understanding the bactericidal mechanism of NTS in nature is essential. The current mechanistic explanations on natural bactericidal activity of nanopillars have not utilized recent advances in microscopy to study the natural interaction. This research reveals the natural bactericidal interaction between E.coli and a dragonfly wing's NTS using advanced microscopy techniques and propose a model. Contrary to the existing mechanistic models, this experimental approach demonstrated that the NTS of dragonfly wings has two prominent nanopillar populations and the resolved interface shows membrane damage occurred without direct contact of the bacterial cell membrane with the nanopillars. We propose that the bacterial membrane damage is initiated by a combination of strong adhesion between nanopillars and bacterium EPS layer as well as shear force when immobilised bacterium attempt to move on the NTS. These findings could help guide the design of novel bio-mimetic nanomaterials by maximising the synergies between both biochemical and mechanical bactericidal effects.Nano-textured surfaces (NTS) are critical to organisms as self-adaptation and survival tools. These NTS have been actively mimicked in the process of developing bactericidal surfaces for diverse biomedical and hygiene applications. To design and fabricate bactericidal topographies effectively for various applications, understanding the bactericidal mechanism of NTS in nature is essential. The current mechanistic explanations on natural bactericidal activity of nanopillars have not utilized recent advances in microscopy to study the natural interaction. This research reveals the natural bactericidal interaction between E.coli and a dragonfly wing's NTS using advanced microscopy techniques and propose a model. Contrary to the existing mechanistic models, this experimental approach demonstrated that the NTS of dragonfly wings has two prominent nanopillar populations and the resolved interface shows membrane damage occurred without direct contact of the bacterial cell membrane with the nanopillars. We propose that the bacterial membrane damage is initiated by a combination of strong adhesion between nanopillars and bacterium EPS layer as well as shear force when immobilised bacterium attempt to move on the NTS. These findings could help guide the design of novel bio-mimetic nanomaterials by maximising the synergies between both biochemical and mechanical bactericidal effects.

Bactericidal effects of natural nanotopography of dragonfly wing on Escherichia coli

Bacterial adhesion to biomaterials: What regulates this attachment? A review.

The growing increase in antibiotic-resistant bacteria has led to the search for new antibacterial agents capable of overcoming the resistance problem. In recent years, nanoparticles (NPs) have been increasingly used to target bacteria as an alternative to antibiotics. The most promising nanomaterials for biomedical applications are metal and metal oxide NPs, due to their intrinsic antibacterial activity. Although NPs show interesting antibacterial properties, the mechanisms underlying their action are still poorly understood, limiting their use in clinical applications. In this review, an overview of the mechanisms underlying the antibacterial activity of metal and metal oxide NPs will be provided, relating their efficacy to: (i) bacterial strain; (ii) higher microbial organizations (biofilm); (iii) and physico-chemical properties of NPs. In addition, bacterial resistance strategies will be also discussed to better evaluate the feasibility of the different treatments adopted in the clinical safety fields. Finally, a wide analysis on recent biomedical applications of metal and metal oxide NPs with antibacterial activity will be provided.

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Metal-Based Nanoparticles: Antibacterial Mechanisms and Biomedical Application

A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include pathogenic bacteria that can serve as a reservoir for persistent infections, and are culpable for leading to a broad spectrum of chronic illnesses and emergence of antibiotic resistance making them difficult to be treated. The absence of biofilm-targeting antibiotics in the drug discovery pipeline indicates an unmet opportunity for designing new biofilm inhibitors as antimicrobial agents using various strategies and targeting distinct stages of biofilm formation. The strategies available to control biofilm formation include targeting the enzymes and proteins specific to the microorganism and those involved in the adhesion pathways leading to formation of resistant biofilms. This review primarily focuses on the recent strategies and advances responsible for identifying a myriad of antibiofilm agents and their mechanism of biofilm inhibition, including extracellular polymeric substance synthesis inhibitors, adhesion inhibitors, quorum sensing inhibitors, efflux pump inhibitors, and cyclic diguanylate inhibitors. Furthermore, we present the structure–activity relationships (SAR) of these agents, including recently discovered biofilm inhibitors, nature-derived bioactive scaffolds, synthetic small molecules, antimicrobial peptides, bioactive compounds isolated from fungi, non-proteinogenic amino acids and antibiotics. We hope to fuel interest and focus research efforts on the development of agents targeting the uniquely complex, physical and chemical heterogeneous biofilms through a multipronged approach and combinatorial therapeutics for a more effective control and management of biofilms across diseases.

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Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

Chronic and recurrent bacterial infections are frequently associated with the formation of biofilms on biotic or abiotic materials that are composed of mono- or multi-species cultures of bacteria/fungi embedded in an extracellular matrix produced by the microorganisms. Biofilm formation is, among others, regulated by quorum sensing (QS) which is an interbacterial communication system usually composed of two-component systems (TCSs) of secreted autoinducer compounds that activate signal transduction pathways through interaction with their respective receptors. Embedded in the biofilms, the bacteria are protected from environmental stress stimuli, and they often show reduced responses to antibiotics, making it difficult to eradicate the bacterial infection. Besides reduced penetration of antibiotics through the intricate structure of the biofilms, the sessile biofilm-embedded bacteria show reduced metabolic activity making them intrinsically less sensitive to antibiotics. Moreover, they frequently express elevated levels of efflux pumps that extrude antibiotics, thereby reducing their intracellular levels. Some efflux pumps are involved in the secretion of QS compounds and biofilm-related materials, besides being important for removing toxic substances from the bacteria. Some efflux pump inhibitors (EPIs) have been shown to both prevent biofilm formation and sensitize the bacteria to antibiotics, suggesting a relationship between these processes. Additionally, QS inhibitors or quenchers may affect antibiotic susceptibility. Thus, targeting elements that regulate QS and biofilm formation might be a promising approach to combat antibiotic-resistant biofilm-related bacterial infections.

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Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Biofilms are structured microbial communities attached to surfaces, which play a significant role in the persistence of biofoulings in both medical and industrial settings. Bacteria in biofilms are mostly embedded in a complex matrix comprised of extracellular polymeric substances that provide mechanical stability and protection against environmental adversities. Once the biofilm is matured, it becomes extremely difficult to kill bacteria or mechanically remove biofilms from solid surfaces. Therefore, interrupting the bacterial surface sensing mechanism and subsequent initial binding process of bacteria to surfaces is essential to effectively prevent biofilm-associated problems. Noting that the process of bacterial adhesion is influenced by many factors, including material surface properties, this review summarizes recent works dedicated to understanding the influences of surface charge, surface wettability, roughness, topography, stiffness, and combination of properties on bacterial adhesion. This review also highlights other factors that are often neglected in bacterial adhesion studies such as bacterial motility and the effect of hydrodynamic flow. Lastly, the present review features recent innovations in nanotechnology-based antifouling systems to engineer new concepts of antibiofilm surfaces.

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Papers

Implication of Surface Properties, Bacterial Motility, and Hydrodynamic Conditions on Bacterial Surface Sensing and Their Initial Adhesion.