Novel Approaches to Combat Medical Device-Associated BioFilms
TL;DR: The challenges associated with the treatment of medical device-associated biofilm infections are summarized and the latest promising approaches aimed at preventing or eradicating these biofilms are highlighted.
Abstract: Biofilms are aggregates formed as a protective survival state by microorganisms to adapt to the environment and can be resistant to antimicrobial agents and host immune responses due to chemical or physical diffusion barriers, modified nutrient environments, suppression of the growth rate within biofilms, and the genetic adaptation of cells within biofilms. With the widespread use of medical devices, medical device-associated biofilms continue to pose a serious threat to human health, and these biofilms have become the most important source of nosocomial infections. However, traditional antimicrobial agents cannot completely eliminate medical device-associated biofilms. New strategies for the treatment of these biofilms and targeting biofilm infections are urgently required. Several novel approaches have been developed and identified as effective and promising treatments. In this review, we briefly summarize the challenges associated with the treatment of medical device-associated biofilm infections and highlight the latest promising approaches aimed at preventing or eradicating these biofilms.
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TL;DR: A comprehensive path is proposed, starting with the photodynamic therapy mechanism, evolution over the years, integration of nanotechnology, and ending with a detailed review of the most important applications of this therapeutic approach.
Abstract: The healing power of light has attracted interest for thousands of years. Scientific discoveries and technological advancements in the field have eventually led to the emergence of photodynamic therapy, which soon became a promising approach in treating a broad range of diseases. Based on the interaction between light, molecular oxygen, and various photosensitizers, photodynamic therapy represents a non-invasive, non-toxic, repeatable procedure for tumor treatment, wound healing, and pathogens inactivation. However, classic photosensitizing compounds impose limitations on their clinical applications. Aiming to overcome these drawbacks, nanotechnology came as a solution for improving targeting efficiency, release control, and solubility of traditional photosensitizers. This paper proposes a comprehensive path, starting with the photodynamic therapy mechanism, evolution over the years, integration of nanotechnology, and ending with a detailed review of the most important applications of this therapeutic approach.
74 citations
TL;DR: In this paper, the authors present the classification of antioxidants and non-enzymatic methods of testing antioxidant capacity in vitro, with particular emphasis on methods based on nanoparticles, and give evaluation methods, reference antioxidants, and details on the preparation of extracts.
Abstract: Natural extracts are the source of many antioxidant substances. They have proven useful not only as supplements preventing diseases caused by oxidative stress and food additives preventing oxidation but also as system components for the production of metallic nanoparticles by the so-called green synthesis. This is important given the drastically increased demand for nanomaterials in biomedical fields. The source of ecological technology for producing nanoparticles can be plants or microorganisms (yeast, algae, cyanobacteria, fungi, and bacteria). This review presents recently published research on the green synthesis of nanoparticles. The conditions of biosynthesis and possible mechanisms of nanoparticle formation with the participation of bacteria are presented. The potential of natural extracts for biogenic synthesis depends on the content of reducing substances. The assessment of the antioxidant activity of extracts as multicomponent mixtures is still a challenge for analytical chemistry. There is still no universal test for measuring total antioxidant capacity (TAC). There are many in vitro chemical tests that quantify the antioxidant scavenging activity of free radicals and their ability to chelate metals and that reduce free radical damage. This paper presents the classification of antioxidants and non-enzymatic methods of testing antioxidant capacity in vitro, with particular emphasis on methods based on nanoparticles. Examples of recent studies on the antioxidant activity of natural extracts obtained from different species such as plants, fungi, bacteria, algae, lichens, actinomycetes were collected, giving evaluation methods, reference antioxidants, and details on the preparation of extracts.
64 citations
TL;DR: In this paper, the authors provided an overview on the formation of bacterial biofilms and its characteristics, burden and evolution with phages and the most recent possible use of phages, and phage-derived enzymes to combat bacteria in biofilm structures.
Abstract: Biofilms are bacterial communities that live in association with biotic or abiotic surfaces and enclosed in an extracellular polymeric substance. Their formation on both biotic and abiotic surfaces, including human tissue and medical device surfaces, pose a major threat causing chronic infections. In addition, current antibiotics and antiseptic agents have shown limited ability to completely remove biofilms. In this review, the authors provide an overview on the formation of bacterial biofilms and its characteristics, burden and evolution with phages. Moreover, the most recent possible use of phages and phage-derived enzymes to combat bacteria in biofilm structures is elucidated. From the emerging results, it can be concluded that despite successful use of phages and phage-derived products in destroying biofilms, they are mostly not adequate to eradicate all bacterial cells. Nevertheless, a combined therapy with the use of phages and/or phage-derived products with other antimicrobial agents including antibiotics, nanoparticles, and antimicrobial peptides may be effective approaches to remove biofilms from medical device surfaces and to treat their associated infections in humans.
29 citations
TL;DR:
Abstract: Acinetobacter baumannii (A. baumannii) is a leading cause of nosocomial infections as this pathogen has certain attributes that facilitate the subversion of natural defenses of the human body. A. baumannii acquires antibiotic resistance determinants easily and can thrive on both biotic and abiotic surfaces. Different resistance mechanisms or determinants, both transmissible and non-transmissible, have aided in this victory over antibiotics. In addition, the propensity to form biofilms (communities of organism attached to a surface) allows the organism to persist in hospitals on various medical surfaces (cardiac valves, artificial joints, catheters, endotracheal tubes, and ventilators) and also evade antibiotics simply by shielding the bacteria and increasing its ability to acquire foreign genetic material through lateral gene transfer. The biofilm formation rate in A. baumannii is higher than in other species. Recent research has shown how A. baumannii biofilm-forming capacity exerts its effect on resistance phenotypes, development of resistome, and dissemination of resistance genes within biofilms by conjugation or transformation, thereby making biofilm a hotspot for genetic exchange. Various genes control the formation of A. baumannii biofilms and a beneficial relationship between biofilm formation and “antimicrobial resistance” (AMR) exists in the organism. This review discusses these various attributes of the organism that act independently or synergistically to cause hospital infections. Evolution of AMR in A. baumannii, resistance mechanisms including both transmissible (hydrolyzing enzymes) and non-transmissible (efflux pumps and chromosomal mutations) are presented. Intrinsic factors [biofilm-associated protein, outer membrane protein A, chaperon-usher pilus, iron uptake mechanism, poly-β-(1, 6)-N-acetyl glucosamine, BfmS/BfmR two-component system, PER-1, quorum sensing] involved in biofilm production, extrinsic factors (surface property, growth temperature, growth medium) associated with the process, the impact of biofilms on high antimicrobial tolerance and regulation of the process, gene transfer within the biofilm, are elaborated. The infections associated with colonization of A. baumannii on medical devices are discussed. Each important device-related infection is dealt with and both adult and pediatric studies are separately mentioned. Furthermore, the strategies of preventing A. baumannii biofilms with antibiotic combinations, quorum sensing quenchers, natural products, efflux pump inhibitors, antimicrobial peptides, nanoparticles, and phage therapy are enumerated.
25 citations
TL;DR: In this paper, the authors presented a fundamental characterization study to show differences between biofilms formed by Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Pseudomonas aeruginosa, and the yeast-type Candida albicans using synchrotron macro attenuated total reflectance Fourier transform infrared (ATR-FTIR) microspectroscopy.
Abstract: Biofilms are assemblages of microbial cells, extracellular polymeric substances (EPS), and other components extracted from the environment in which they develop. Within biofilms, the spatial distribution of these components can vary. Here we present a fundamental characterization study to show differences between biofilms formed by Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Pseudomonas aeruginosa, and the yeast-type Candida albicans using synchrotron macro attenuated total reflectance-Fourier transform infrared (ATR-FTIR) microspectroscopy. We were able to characterise the pathogenic biofilms’ heterogeneous distribution, which is challenging to do using traditional techniques. Multivariate analyses revealed that the polysaccharides area (1200–950 cm−1) accounted for the most significant variance between biofilm samples, and other spectral regions corresponding to amides, lipids, and polysaccharides all contributed to sample variation. In general, this study will advance our understanding of microbial biofilms and serve as a model for future research on how to use synchrotron source ATR-FTIR microspectroscopy to analyse their variations and spatial arrangements.
17 citations
References
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TL;DR: The functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth are described.
Abstract: The microorganisms in biofilms live in a self-produced matrix of hydrated extracellular polymeric substances (EPS) that form their immediate environment. EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide the mechanical stability of biofilms, mediate their adhesion to surfaces and form a cohesive, three-dimensional polymer network that interconnects and transiently immobilizes biofilm cells. In addition, the biofilm matrix acts as an external digestive system by keeping extracellular enzymes close to the cells, enabling them to metabolize dissolved, colloidal and solid biopolymers. Here we describe the functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth.
7,041 citations
TL;DR: It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments.
Abstract: Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.
6,170 citations
TL;DR: The results reviewed in this article indicate that the formation of biofilms serves as a new model system for the study of microbial development.
Abstract: ▪ Abstract Biofilms can be defined as communities of microorganisms attached to a surface. It is clear that microorganisms undergo profound changes during their transition from planktonic (free-swimming) organisms to cells that are part of a complex, surface-attached community. These changes are reflected in the new phenotypic characteristics developed by biofilm bacteria and occur in response to a variety of environmental signals. Recent genetic and molecular approaches used to study bacterial and fungal biofilms have identified genes and regulatory circuits important for initial cell-surface interactions, biofilm maturation, and the return of biofilm microorganisms to a planktonic mode of growth. Studies to date suggest that the planktonic-biofilm transition is a complex and highly regulated process. The results reviewed in this article indicate that the formation of biofilms serves as a new model system for the study of microbial development.
3,321 citations
TL;DR: How basic science studies are elucidating the molecular details of the crosstalk that occurs at the host–pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs is discussed.
Abstract: Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
2,251 citations
TL;DR: This review summarizes the diagnostic challenges and explains the approaches to managing infections that are associated with various devices, including prosthetic heart valves, vascular grafts, pacemakers and defibrillators, and joint prostheses.
Abstract: About half of all nosocomial infections are associated with indwelling devices. Infections associated with implanted surgical devices are particularly difficult to deal with because they can require prolonged antibiotic treatment and repeated surgical procedures. This review summarizes the diagnostic challenges and explains the approaches to managing infections that are associated with various devices, including prosthetic heart valves, vascular grafts, pacemakers and defibrillators, and joint prostheses.
2,062 citations