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      New Perspectives on the Use of Phytochemicals as an Emergent Strategy to Control Bacterial Infections Including Biofilms

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          Abstract

          The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs not as vulnerable as the current ones to bacterial resistance mechanisms, and also able to target bacteria in biofilms. Natural products, especially those obtained from plants, have proven to be outstanding compounds with unique properties, making them perfect candidates for these much-needed therapeutics. This review presents the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. Further, the difficulties associated with the use of the existing antibiotics in the treatment of biofilm-related infections are described. To counteract the biofilm resistance problems, innovative strategies are suggested based on literature data. Among the proposed strategies, the use of phytochemicals to inhibit or eradicate biofilms is highlighted. An overview on the use of phytochemicals to interfere with bacterial quorum sensing (QS) signaling pathways and underlying phenotypes is provided. The use of phytochemicals as chelating agents and efflux pump inhibitors is also reviewed.

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          Plant pathogens and integrated defence responses to infection.

          Plants cannot move to escape environmental challenges. Biotic stresses result from a battery of potential pathogens: fungi, bacteria, nematodes and insects intercept the photosynthate produced by plants, and viruses use replication machinery at the host's expense. Plants, in turn, have evolved sophisticated mechanisms to perceive such attacks, and to translate that perception into an adaptive response. Here, we review the current knowledge of recognition-dependent disease resistance in plants. We include a few crucial concepts to compare and contrast plant innate immunity with that more commonly associated with animals. There are appreciable differences, but also surprising parallels.
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            Extended-Spectrum β-Lactamases: a Clinical Update

            Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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              Call of the wild: antibiotic resistance genes in natural environments.

              Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of resistance determinants are poorly understood. The origins of antibiotic resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens. This Review explores the presence and spread of antibiotic resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                05 July 2016
                July 2016
                : 21
                : 7
                : 877
                Affiliations
                [1 ]LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal; anabreu@ 123456fe.up.pt (A.C.A.); cdias@ 123456utad.pt (C.D.)
                [2 ]CIQUP, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, s/n, Porto 4169-007, Portugal; fborges@ 123456fc.up.pt
                [3 ]CECAV-Veterinary and Animal Science Research Center, Department of Veterinary Science, University of Trás-os-Montes e Alto Douro, Apartado 1013, Vila Real 5001-801, Portugal; saavedra@ 123456utad.pt
                Author notes
                [* ]Correspondence: apborges@ 123456fe.up.pt (A.B.); mvs@ 123456fe.up.pt (M.S.); Tel.: +351-225-084-968 (A.B.); +351-225-081-654 (M.S.)
                Article
                molecules-21-00877
                10.3390/molecules21070877
                6274140
                27399652
                2f347f4c-d262-494f-b861-cbfab3be1941
                © 2016 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
                : 31 May 2016
                : 29 June 2016
                Categories
                Review

                antibiotic adjuvants,antibiofilm strategies,multidrug resistance,efflux pump inhibition,metal chelators,plant compounds,quorum sensing inhibition

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