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      Biofilm formation mechanisms and targets for developing antibiofilm agents

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          Abstract

          Biofilms are communities of microorganisms that are attached to a surface and play a significant role in the persistence of bacterial infections. Bacteria within a biofilm are several orders of magnitude more resistant to antibiotics, compared with planktonic bacteria. Thus far, no drugs are in clinical use that specifically target bacterial biofilms. This is probably because until recently the molecular details of biofilm formation were poorly understood. Bacteria integrate information from the environment, such as quorum-sensing autoinducers and nutrients, into appropriate biofilm-related gene expression, and the identity of the key players, such as cyclic dinucleotide second messengers and regulatory RNAs are beginning to be uncovered. Herein, we highlight the current understanding of the processes that lead to biofilm formation in many bacteria.

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          Most cited references152

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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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            Bacterial biofilms: a common cause of persistent infections.

            Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
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              Persister cells, dormancy and infectious disease.

              Kim Lewis (2007)
              Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.
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                Author and article information

                Journal
                Future Medicinal Chemistry
                Future Medicinal Chemistry
                Future Science Ltd
                1756-8919
                1756-8927
                March 2015
                March 2015
                : 7
                : 4
                : 493-512
                Affiliations
                [1 ]Department of Chemistry & Biochemistry, University of Maryland, College Park, MD 20742, USA
                [2 ]Department of Natural Sciences, Bowie State University, 14000 Jericho Park Road, Bowie, MD 20715, USA
                Article
                10.4155/fmc.15.6
                25875875
                11486d5e-ce08-4bbd-8383-0ce6701a5bd8
                © 2015
                History

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