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      Promising Therapeutic Strategies Against Microbial Biofilm Challenges

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          Abstract

          Biofilms are communities of microorganisms that are attached to a biological or abiotic surface and are surrounded by a self-produced extracellular matrix. Cells within a biofilm have intrinsic characteristics that are different from those of planktonic cells. Biofilm resistance to antimicrobial agents has drawn increasing attention. It is well-known that medical device- and tissue-associated biofilms may be the leading cause for the failure of antibiotic treatments and can cause many chronic infections. The eradication of biofilms is very challenging. Many researchers are working to address biofilm-related infections, and some novel strategies have been developed and identified as being effective and promising. Nevertheless, more preclinical studies and well-designed multicenter clinical trials are critically needed to evaluate the prospects of these strategies. Here, we review information about the mechanisms underlying the drug resistance of biofilms and discuss recent progress in alternative therapies and promising strategies against microbial biofilms. We also summarize the strengths and weaknesses of these strategies in detail.

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          Most cited references159

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          Microbial biofilms.

          Direct observations have clearly shown that biofilm bacteria predominate, numerically and metabolically, in virtually all nutrient-sufficient ecosystems. Therefore, these sessile organisms predominate in most of the environmental, industrial, and medical problems and processes of interest to microbiologists. If biofilm bacteria were simply planktonic cells that had adhered to a surface, this revelation would be unimportant, but they are demonstrably and profoundly different. We first noted that biofilm cells are at least 500 times more resistant to antibacterial agents. Now we have discovered that adhesion triggers the expression of a sigma factor that derepresses a large number of genes so that biofilm cells are clearly phenotypically distinct from their planktonic counterparts. Each biofilm bacterium lives in a customized microniche in a complex microbial community that has primitive homeostasis, a primitive circulatory system, and metabolic cooperativity, and each of these sessile cells reacts to its special environment so that it differs fundamentally from a planktonic cell of the same species.
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            Physiological heterogeneity in biofilms.

            Biofilms contain bacterial cells that are in a wide range of physiological states. Within a biofilm population, cells with diverse genotypes and phenotypes that express distinct metabolic pathways, stress responses and other specific biological activities are juxtaposed. The mechanisms that contribute to this genetic and physiological heterogeneity include microscale chemical gradients, adaptation to local environmental conditions, stochastic gene expression and the genotypic variation that occurs through mutation and selection. Here, we discuss the processes that generate chemical gradients in biofilms, the genetic and physiological responses of the bacteria as they adapt to these gradients and the techniques that can be used to visualize and measure the microscale physiological heterogeneities of bacteria in biofilms.
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              Oral multispecies biofilm development and the key role of cell-cell distance.

              Growth of oral bacteria in situ requires adhesion to a surface because the constant flow of host secretions thwarts the ability of planktonic cells to grow before they are swallowed. Therefore, oral bacteria evolved to form biofilms on hard tooth surfaces and on soft epithelial tissues, which often contain multiple bacterial species. Because these biofilms are easy to study, they have become the paradigm of multispecies biofilms. In this Review we describe the factors involved in the formation of these biofilms, including the initial adherence to the oral tissues and teeth, cooperation between bacterial species in the biofilm, signalling between the bacteria and its role in pathogenesis, and the transfer of DNA between bacteria. In all these aspects distance between cells of different species is integral for oral biofilm growth.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                28 July 2020
                2020
                : 10
                : 359
                Affiliations
                [1] 1Department of Infectious Diseases, First Hospital of Jilin University , Changchun, China
                [2] 2Department of Pediatrics, University of Oklahoma Health Sciences Center , Oklahoma City, OK, United States
                Author notes

                Edited by: D. Scott Merrell, Uniformed Services University, United States

                Reviewed by: Aruni Wilson, Loma Linda University, United States; Robert M. Shanks, University of Pittsburgh, United States

                *Correspondence: Yang Wang wyang@ 123456jlu.edu.cn

                This article was submitted to Bacteria and Host, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2020.00359
                7399198
                32850471
                144b3176-dd37-4bed-a2d9-b2a27b264983
                Copyright © 2020 Zhang, Li, Yu and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 March 2020
                : 10 June 2020
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 196, Pages: 16, Words: 13578
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Categories
                Cellular and Infection Microbiology
                Review

                Infectious disease & Microbiology
                biofilm,antibiotic resistance,antimicrobial peptides,nanotechnology,combination therapies

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