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      Anti-Biofilm Molecules Targeting Functional Amyloids

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          Abstract

          The choice of an effective therapeutic strategy in the treatment of biofilm-related infections is a significant issue. Amyloids, which have been historically related to human diseases, are now considered to be prevailing structural components of the biofilm matrix in a wide range of bacteria. This assumption creates the potential for an exciting research area, in which functional amyloids are considered to be attractive targets for drug development to dissemble biofilm structures. The present review describes the best-characterized bacterial functional amyloids and focuses on anti-biofilm agents that target intrinsic and facultative amyloids. This study provides a better understanding of the different modes of actions of the anti-amyloid molecules to inhibit biofilm formation. This information can be further exploited to improve the therapeutic strategies to combat biofilm-related infections.

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          Most cited references138

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          The biofilm matrix.

          The microorganisms in biofilms live in a self-produced matrix of hydrated extracellular polymeric substances (EPS) that form their immediate environment. EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide the mechanical stability of biofilms, mediate their adhesion to surfaces and form a cohesive, three-dimensional polymer network that interconnects and transiently immobilizes biofilm cells. In addition, the biofilm matrix acts as an external digestive system by keeping extracellular enzymes close to the cells, enabling them to metabolize dissolved, colloidal and solid biopolymers. Here we describe the functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth.
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            Antimicrobial resistance: a global multifaceted phenomenon.

            Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century. The first World Health Organization (WHO) Global report on surveillance of AMR, published in April 2014, collected for the first time data from national and international surveillance networks, showing the extent of this phenomenon in many parts of the world and also the presence of large gaps in the existing surveillance. In this review, we focus on antibacterial resistance (ABR), which represents at the moment the major problem, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of ABR. We describe the health and economic impact of ABR, the principal risk factors for its emergence and, in particular, we illustrate the highlights of four antibiotic-resistant pathogens of global concern - Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis - for whom we report resistance data worldwide. Measures to control the emergence and the spread of ABR are presented.
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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

                Contributors
                Role: Academic Editor
                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                29 June 2021
                July 2021
                : 10
                : 7
                : 795
                Affiliations
                Instituto de Agrobiotecnología (Idab), CSIC-Gobierno de Navarra, 31192 Navarra, Spain; leticia.matilla@ 123456unavarra.es (L.M.-C.); a.toledo.arana@ 123456csic.es (A.T.-A.)
                Author notes
                [* ]Correspondence: jaione.valle@ 123456csic.es
                Author information
                https://orcid.org/0000-0003-1822-0151
                https://orcid.org/0000-0001-8148-6281
                Article
                antibiotics-10-00795
                10.3390/antibiotics10070795
                8300730
                34210036
                02a1ee84-ebb8-428b-a906-a8fd53789059
                © 2021 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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2021
                : 25 June 2021
                Categories
                Review

                biofilm,amyloids,antibiotic resistance,peptides,polyphenols
                biofilm, amyloids, antibiotic resistance, peptides, polyphenols

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