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      Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

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          ABSTRACT

          Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC 50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.

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          Most cited references236

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          Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development.

          The formation of complex bacterial communities known as biofilms begins with the interaction of planktonic cells with a surface in response to appropriate environmental signals. We report the isolation and characterization of mutants of Pseudomonas aeruginosa PA14 defective in the initiation of biofilm formation on an abiotic surface, polyvinylchloride (PVC) plastic. These mutants are designated surface attachment defective (sad ). Two classes of sad mutants were analysed: (i) mutants defective in flagellar-mediated motility and (ii) mutants defective in biogenesis of the polar-localized type IV pili. We followed the development of the biofilm formed by the wild type over 8 h using phase-contrast microscopy. The wild-type strain first formed a monolayer of cells on the abiotic surface, followed by the appearance of microcolonies that were dispersed throughout the monolayer of cells. Using time-lapse microscopy, we present evidence that microcolonies form by aggregation of cells present in the monolayer. As observed with the wild type, strains with mutations in genes required for the synthesis of type IV pili formed a monolayer of cells on the PVC plastic. However, in contrast to the wild-type strain, the type IV pili mutants did not develop microcolonies over the course of the experiments, suggesting that these structures play an important role in microcolony formation. Very few cells of a non-motile strain (carrying a mutation in flgK) attached to PVC even after 8 h of incubation, suggesting a role for flagella and/or motility in the initial cell-to-surface interactions. The phenotype of these mutants thus allows us to initiate the dissection of the developmental pathway leading to biofilm formation.
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            (p)ppGpp: still magical?

            The fundamental details of how nutritional stress leads to elevating (p)ppGpp are questionable. By common usage, the meaning of the stringent response has evolved from the specific response to (p)ppGpp provoked by amino acid starvation to all responses caused by elevating (p)ppGpp by any means. Different responses have similar as well as dissimilar positive and negative effects on gene expression and metabolism. The different ways that different bacteria seem to exploit their capacities to form and respond to (p)ppGpp are already impressive despite an early stage of discovery. Apparently, (p)ppGpp can contribute to regulation of many aspects of microbial cell biology that are sensitive to changing nutrient availability: growth, adaptation, secondary metabolism, survival, persistence, cell division, motility, biofilms, development, competence, and virulence. Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains.
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              Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators.

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                Author and article information

                Journal
                Virulence
                Virulence
                KVIR
                kvir20
                Virulence
                Taylor & Francis
                2150-5594
                2150-5608
                2018
                31 March 2017
                31 March 2017
                : 9
                : 1
                : 522-554
                Affiliations
                [a ]Department of Biochemistry, Central University of Rajasthan , Ajmer, India
                [b ]Microbial Biofilm Laboratory, IRCCS Fondazione Santa Lucia , Rome, Italy
                Author notes
                CONTACT Vishvanath Tiwari vishvanath7@ 123456yahoo.co.in Department of Biochemistry, Central University of Rajasthan , Ajmer-305817, India
                [†]

                Authors contributed equally to work.

                Article
                1313372
                10.1080/21505594.2017.1313372
                5955472
                28362216
                37f11625-2412-4120-8e6e-d5b527eea200
                © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 September 2016
                : 24 March 2017
                : 25 March 2017
                Page count
                Figures: 10, Tables: 3, Equations: 0, References: 298, Pages: 33
                Funding
                Funded by: DST | Science and Engineering Research Board (SERB)
                Award ID: SB/YS/LS-07/2014
                VT would like to thanks SERB, DST, India for Start Up grant (SB/YS/LS-07/2014). MT would like to thanks Central University of Rajasthan for the Ph.D. fellowship.
                Categories
                Review

                Infectious disease & Microbiology
                anti-biofilm molecules,antimicrobial peptide,biofilm formation,biofilm model,drug resistance,herbal molecules

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