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      Biofilms in Diabetic Foot Ulcers: Significance and Clinical Relevance

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          Abstract

          Foot infections are the main disabling complication in patients with diabetes mellitus. These infections can lead to lower-limb amputation, increasing mortality and decreasing the quality of life. Biofilm formation is an important pathophysiology step in diabetic foot ulcers (DFU)—it plays a main role in the disease progression and chronicity of the lesion, the development of antibiotic resistance, and makes wound healing difficult to treat. The main problem is the difficulty in distinguishing between infection and colonization in DFU. The bacteria present in DFU are organized into functionally equivalent pathogroups that allow for close interactions between the bacteria within the biofilm. Consequently, some bacterial species that alone would be considered non-pathogenic, or incapable of maintaining a chronic infection, could co-aggregate symbiotically in a pathogenic biofilm and act synergistically to cause a chronic infection. In this review, we discuss current knowledge on biofilm formation, its presence in DFU, how the diabetic environment affects biofilm formation and its regulation, and the clinical implications.

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          Most cited references121

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          Diabetic Foot Ulcers and Their Recurrence.

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            Bacterial biofilms: from the natural environment to infectious diseases.

            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.
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              Bacterial quorum sensing: its role in virulence and possibilities for its control.

              Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                14 October 2020
                October 2020
                : 8
                : 10
                : 1580
                Affiliations
                [1 ]Virulence Bactérienne et Maladies Infectieuses, INSERM U1047, Université de Montpellier, 30908 Nîmes, France; cassandra.pouget@ 123456gmail.com
                [2 ]Virulence Bactérienne et Maladies Infectieuses, INSERM U1047, Université de Montpellier, Service de Microbiologie et Hygiène Hospitalière, Clinique du Pied Gard Occitanie, CHU Nîmes, 30029 Nîmes, France; catherine.remy@ 123456chu-nimes.fr (C.D.-R.); alix.pantel@ 123456chu-nimes.fr (A.P.)
                [3 ]Virulence Bactérienne et Maladies Infectieuses, INSERM U1047, Université de Montpellier, Service des Maladies Métaboliques et Endocriniennes, Clinique du Pied Gard Occitanie, CHU Nîmes, 30240 Le Grau du Roi, France; sophie.schuldiner@ 123456chu-nimes.fr
                [4 ]Virulence Bactérienne et Maladies Infectieuses, INSERM, Université de Montpellier, Service des Maladies Infectieuses et Tropicales, Clinique du Pied Gard Occitanie, CHU Nîmes, 30029 Nîmes, France; albert.sotto@ 123456chu-nimes.fr
                Author notes
                [* ]Correspondence: jean.philippe.lavigne@ 123456chu-nimes.fr ; Tel.: +33-466-683-202; Fax: +33-466-684-254
                Author information
                https://orcid.org/0000-0002-9484-0304
                Article
                microorganisms-08-01580
                10.3390/microorganisms8101580
                7602394
                33066595
                c0716b2a-587c-42ba-8f93-19687aeef594
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 September 2020
                : 11 October 2020
                Categories
                Review

                biofilm,commensal bacteria,diabetic foot infection,diabetic foot ulcer,pathogenic bacteria,pathogroups

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