Medical Implications of Biofilms
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Outside your mouth, biofilm-related health problems are more common than you might think. What's alarming about biofilm infections is the fact that some aren't easy to get rid of and can be tolerant of antimicrobial treatments such as antibiotics. This means some medicines won't work for people who are ill from biofilm infections. Biofilms can cause a variety of health problems, ranging from a common earache to a specific bacterial infection found in people living with a genetic disease called cystic fibrosis.
But biofilms are particularly an area of concern for patients with implanted medical devices. They have been found on some devices more than others, including:.
Annual epidemiological report on communicable diseases in Europe. Microorganisms are able to adhere to various surfaces and to form there a three-dimensional structure known as biofilm. They simultaneously assist the development of biofilms, but also prevent microorganisms and undesirable substances and molecules from crossing into the body from the colon. Aminoglycoside antibiotics induce bacterial biofilm formation. Animal Science and Biotechnologies. Endogenously acquired antigen e.
In hospital settings, microbes that form biofilms usually enter a patient's body from being transferred on the implant or inside the patient from the patient himself, visitors or hospital staff beforehand. Certain types of biofilms, such as those from the genus Staphylococcus , are more harmful because they release toxins and can be highly resistant to antibiotics, especially if they form biofilms in a patient's body see How Staph Infections Work to read more. Getting rid of biofilms, especially staph bacteria, can be a challenge for patients with implants, but there are a few options.
The ever-changing role of biofilms in plastic surgery. A survival and resistance mechanism of microorganisms. Biofilms, infection and antimicrobial therapy. Detection of biofilm in wounds as an early indicator for risk for tissue infection and wound chronicity. The role of bacterial biofilms in chronic infections.
Dower R, Turner ML. Pilot study of timing of biofilm formation on closed suction wound drains. Rouabhia M, Chmielewski W. Diseases associated with oral polymicrobial biofilms. Microbial biofilms in dental medicine in reference to implanto-prostethic rehabilitation. In vitro and in vivo investigation of the influence of implant surface on the formation of bacterial biofilm in mammary implants.
Bacterial biofilm infection detected in breast implant—associated anaplastic large-cell lymphoma. Increased resistance of contact lens—related bacterial biofilms to antimicrobial activity of soft contact lens care solutions. Dexamethasone diffusion across contact lenses is inhibited by Staphylococcus epidermidis biofilms in vitro. Scanning electron microscopic analysis of biofilm formation in explanted human Boston type I keratoprostheses. Edited by Blackwell Publishing Ltd, ; Anti-biofilm Activity as a Health Issue.
Advanced endotracheal tube biofilm stage, not duration of intubation, is related to pneumonia. J Trauma Acute Care Surg. Linezolid limits burden of methicillin-resistant Staphylococcus aureus in biofilm of tracheal tubes. Prevention of waterborne infections — what can be done?. Int J Infect Control. Review drug resistance of bacterial dental biofilm and the potential use of natural compounds as alternative for prevention and treatment. Novel rat model of methicillin-resistant Staphylococcus aureus—infected silicone breast implants: A study of biofilm pathogenesis.
Lazar V, Chifiriuc MC. Science against microbial pathogens: Current Pharmaceutical Design, ;21 1: The role of bacterial biofilms in device-associated infection. Niu C, Gilbert ES. Colorimetric method for identifying plant essential oil components that affect biofilm formation and structure. Coenye T, Nelisa HJ.
In vitro and in vivo model systems to study microbial biofilm formation.
Romanian Journal of Laboratory Medicine
Biofilm formation of Staphylococcus, Streptococcus, Pasteurella and Neisseria strains. Fluorescein groups allowed the imaging of bound opsonin plus they are recognized by antifluorescein Mab, which promoted binding to macrophage.
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Flow cytometry revealed that bi-specific polymer-labeled S. The Taylor group, in series of elegant papers, reports the use of several different bi-specific fusion proteins BiFPs that enhanced phagocytosis by macrophage of various pathogens, including: In all cases, BiFPs consisted of 1 a molecule that recognizes a surface marker on the pathogen that was chemically coupled with 2 a Mab that is specific to the complement receptor 1 CR1 present on primate erythrocytes.
[Biofilms and their significance in medical microbiology].
In in vitro and in vivo studies, these works from the Taylor groups have shown that BiFPs promote binding of the target pathogen first to circulating erythrocytes, which then enhances macrophage phagocytosis of the bacteria. BiFP mediated phagocytosis did not apparently harm the erythrocyte, as verified in both in vitro and in vivo experiments Kuhn et al. The Kobayashi work selectively targeted Fc receptors that were dominant on PMNs collected from gingival crevicular fluid of chronic periodontitis patients versus Fc receptors dominant on peripheral blood PMNs.
Data show that PMNs exhibited a higher capacity to phagocytose and kill P.
Use of bi-specific fusion proteins to opsonize pathogenic bacteria and enhance phagocytosis. Imagine a biomedical device that would be capable of generating a life-long protection for itself against infection? Our research group is developing a biomaterials platform that will engineer infection immunity by releasing in multiple waves, vaccines that have as antigen targets—those bacterial surface structures used for bacterial specific adhesion Fig.
The goal of any vaccine is to produce a long-term protective immune response against a pathogen. For most bacteria, initial attachment to a eukaryotic cell surface or ligand-coated biomedical device leads to biofilm formation, then up-regulation of virulence factors leading to infection. Both an innate and an induced antibody response could prevent attachment and abrogate colonization. Given that bacterial specific adhesion can trigger expression of many virulence factors leading to acute and chronic inflammation, a vaccine approach that blocks bacterial adhesion may have multiple advantages.
Recent research has greatly expanded the molecular details of the specific adhesin: Thus, the concept of biomaterials designed to engineer infection immunity, targeting specific adhesins, could be applied to numerous situations. There are essentially three ways to activate a dendritic cell to present antigen with the subsequent immune response being dependent upon the form of the antigen Fig.
Endogenously acquired antigen e. In contrast to protein vaccines, DNA- or RNA-based vaccines can provide the ability to potentially generate both a strong cytotoxic T cell response and humoral response. Antigen presentation and pathways of vaccine response.
Antigen can be secreted not shown and subsequently taken up by another DCs as an exogenous antigen. Upon internalization of a pDNA vaccine carrier by dendritic cells, the carrier must escape endosomal entrapment or be degraded, the carrier must release the pDNA into the cytoplasm, and then the pDNA must be incorporated into the dendritic nucleus for expression. DNA vaccines have certain advantages over protein antigens including: Disadvantages of DNA vaccines include: Since RNA does not require nuclear incorporation, expression of antigen in transfected cells occurs much faster than with pDNA.
Potentially dangerous side effects are reduced since eukaryotic promoters needed for pDNA are not present in RNA constructs. One main drawback to both DNA- and RNA-vaccines is that the efficiency of naked oligonucleotide transfection is very low compared to viral systems due to lack of protection from systemic nucleases, inability to migrate through cell membranes, or entrapment and degradation within endosomes. Consequently, non-viral gene constructs typically require some type of polymer delivery system.
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The reader is directed to a number of excellent reviews on the subject of polymer gene delivery published by Dang and Leong , Gao et al. We are currently developing a platform of polymer constructs that would release condensed RNA vaccines meant to transfect dendritic cells arriving upon implantation of a biomedical device. Our polymer constructs will release nanoparticles of condensed DNA or mRNA vaccine that will target a selected adhesion protein employed by the microorganism to initiate colonization.
Such targets could be the fibronectin binding receptors on S. One distinct advantage of nucleotide transfection of dendritic cells vs.
We are currently developing mRNA vaccines anti- to the S. As our population ages, there will be an increase in the number of people experiencing hospitalization and receiving short- or long-term biomedical implants. As engineered biomaterials and tissue regenerative medicine advance, an increasing portion of the population will receive one or multiple biomedical devices, ranging from disposable contact lenses, dental implants, orthopedic implants, and vascular grafts to tissue engineered livers, small diameter vascular grafts that promote stem cells differentiation into endothelial cells, and polymer transfection systems that deliver micro-RNA knockout therapy to control chronic inflammation.
The current health care approach to clean and sterilize has done little to prevent an epidemic in nosocomial infections. Biomaterials technologies employing disinfectant rinses, tethered or release antibiotics have also done little to reduce this epidemic and may have contributed to the raise of antibiotic resistant bacteria. Increasing scientific research over the past 10 years in biofilm formation has provided a wealth of possible targets with which to prevent or eradicate biofilm infections.
Advances in the understanding of biofilm formation, coupled with emerging engineered biomaterials, provide many potential platforms and strategies to prevent or significantly reduce biofilm infections in susceptible populations. National Center for Biotechnology Information , U. Author manuscript; available in PMC Jul 7. The publisher's final edited version of this article is available at Biotechnol Bioeng. See other articles in PMC that cite the published article.
Abstract For more than two decades, Biotechnology and Bioengineering has documented research focused on natural and engineered microbial biofilms within aquatic and subterranean ecosystems, wastewater and waste-gas treatment systems, marine vessels and structures, and industrial bioprocesses.
Introduction Biofilms can kill. Open in a separate window. Processes Governing Biofilm Formation Biofilm formation comprises a number of physical, biological, and chemical processes Fig. Infection, Inflammation, and Host Immune Response Regrettably the majority, if not all , studies of immune response to bacteria have been carried out using intact freely suspended bacterial cell cultures or bacterial cell components isolated from suspended bacterial cells. Immune Cell Response The immune system has evolved to protect the host from infection in two ways: Immune Evasion by Bacteria The primary defense against infection is the innate immunity provided by neutrophils, macrophages, and dendritic cells.
Immune Cell Interactions As indicated above, freely suspended microorganisms have evolved a multitude of ways to avoid detection by the immune system. Controlling Medical Biofilms Good Intentions Gone Bad Since native immunity can be circumvented or compromised by drugs or disease , the medical profession has been attempting to eradicate biofilm-based infections by resorting to disinfectants and antibiotics.
New Directions in Medical Biofilm Control Traditional treatment of microbial infections is based on compounds that kill or inhibit growth of the microbe. Iron Metabolism Interference Iron is critical for bacterial growth and the function of key metabolic enzymes Ankenbauer et al. Engineering Infection Immunity Imagine a biomedical device that would be capable of generating a life-long protection for itself against infection?
Concluding Remarks As our population ages, there will be an increase in the number of people experiencing hospitalization and receiving short- or long-term biomedical implants. Concise review of mechanisms of bacterial adhesion to biomaterial surfaces. J Biomed Mater Res. Biological responses to materials. Annu Rev Mater Res. A novel phenotype for an activated macrophage: The type 2 activated macrophage.
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Zentralbl Bakteriol Mikrobiol Hyg [A] ; Diagnosis of periprosthetic infection. J Bone Joint Surg Am. Mobilization of broad host range plasmid from Pseudomonas putida to established biofilm of Bacillus azotoformans.
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Microbial biofilm in human health - an updated theoretical and practical insight
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