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      Strategies for combating bacterial biofilm infections

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          Abstract

          Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.

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          Most cited references68

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          Biofilms and device-associated infections.

          Microorganisms commonly attach to living and nonliving surfaces, including those of indwelling medical devices, and form biofilms made up of extracellular polymers. In this state, microorganisms are highly resistant to antimicrobial treatment and are tenaciously bound to the surface. To better understand and control biofilms on indwelling medical devices, researchers should develop reliable sampling and measurement techniques, investigate the role of biofilms in antimicrobial drug resistance, and establish the link between biofilm contamination and patient infection.
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            Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies.

            Bacteria have evolved the ability to form multicellular, surface-adherent communities called biofilms that allow survival in hostile environments. In clinical settings, bacteria are exposed to various sources of stress, including antibiotics, nutrient limitation, anaerobiosis, heat shock, etc., which in turn trigger adaptive responses in bacterial cells. The combination of this and other defense mechanisms results in the formation of highly (adaptively) resistant multicellular structures that are recalcitrant to host immune clearance mechanisms and very difficult to eradicate with the currently available antimicrobial agents, which are generally developed for the eradication of free-swimming (planktonic) bacteria. However, novel strategies that specifically target the biofilm mode of growth have been recently described, thus providing the basis for future anti-biofilm therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation.

              Quorum sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling quorum-sensing circuits with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Here, we analyze synthetic molecules for inhibition of the two P. aeruginosa quorum-sensing receptors, LasR and RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both the production of the virulence factor pyocyanin and biofilm formation. mBTL also protects Caenorhabditis elegans and human lung epithelial cells from killing by P. aeruginosa. Both LasR and RhlR are partially inhibited by mBTL in vivo and in vitro; however, RhlR, not LasR, is the relevant in vivo target. More potent antagonists do not exhibit superior function in impeding virulence. Because LasR and RhlR reciprocally control crucial virulence factors, appropriately tuning rather than completely inhibiting their activities appears to hold the key to blocking pathogenesis in vivo.
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                Author and article information

                Journal
                Int J Oral Sci
                Int J Oral Sci
                International Journal of Oral Science
                Nature Publishing Group
                1674-2818
                2049-3169
                March 2015
                12 December 2014
                1 March 2015
                : 7
                : 1
                : 1-7
                Affiliations
                [1 ]Department of Clinical Microbiology, Rigshospitalet, University Hospital of Copenhagen , Copenhagen, Denmark
                [2 ]Department of International Health, Immunology & Microbiology, University of Copenhagen , Copenhagen, Denmark
                [3 ]Department of Clinical Microbiology, Slagelse Hospital , Slagelse, Denmark
                Author notes
                [* ]Department of Clinical Microbiology, Rigshospitalet, University Hospital of Copenhagen, Juliane Maries Vej 22 , Copenhagen DK-2100, Denmark. E-mail: szj56@ 123456hotmail.com
                Article
                ijos201465
                10.1038/ijos.2014.65
                4817533
                25504208
                b122b42b-5813-4982-8a39-a083fd09e4c3
                Copyright © 2014 West China School of Stomatology

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 16 July 2014
                Categories
                Review

                Dentistry
                antibiotic resistance,antimicrobial treatments,bacterial biofilm,chronic infection
                Dentistry
                antibiotic resistance, antimicrobial treatments, bacterial biofilm, chronic infection

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