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      Review on plant antimicrobials: a mechanistic viewpoint

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          Abstract

          Microbial resistance to classical antibiotics and its rapid progression have raised serious concern in the treatment of infectious diseases. Recently, many studies have been directed towards finding promising solutions to overcome these problems. Phytochemicals have exerted potential antibacterial activities against sensitive and resistant pathogens via different mechanisms of action. In this review, we have summarized the main antibiotic resistance mechanisms of bacteria and also discussed how phytochemicals belonging to different chemical classes could reverse the antibiotic resistance. Next to containing direct antimicrobial activities, some of them have exerted in vitro synergistic effects when being combined with conventional antibiotics. Considering these facts, it could be stated that phytochemicals represent a valuable source of bioactive compounds with potent antimicrobial activities.

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          The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria.

          Gram-negative bacteria are responsible for a large proportion of antibiotic-resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channels.
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            Natural products as antimicrobial agents

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              Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery.

              Penicillin and related beta-lactams comprise one of our oldest and most widely used antibiotic therapies. These drugs have long been known to target enzymes called penicillin-binding proteins (PBPs) that build the bacterial cell wall. Investigating the downstream consequences of target inhibition and how they contribute to the lethal action of these important drugs, we demonstrate that beta-lactams do more than just inhibit the PBPs as is commonly believed. Rather, they induce a toxic malfunctioning of their target biosynthetic machinery involving a futile cycle of cell wall synthesis and degradation, thereby depleting cellular resources and bolstering their killing activity. Characterization of this mode of action additionally revealed a quality control function for enzymes that cleave bonds in the cell wall matrix. The results thus provide insight into the mechanism of cell wall assembly and suggest how best to interfere with the process for future antibiotic development.
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                Author and article information

                Contributors
                Khamenehbagherib@mums.ac.ir
                IranshahyM@mums.ac.ir
                SoheiliV@mums.ac.ir
                +98-51-31801130 , Fazlis@mums.ac.ir
                Journal
                Antimicrob Resist Infect Control
                Antimicrob Resist Infect Control
                Antimicrobial Resistance and Infection Control
                BioMed Central (London )
                2047-2994
                16 July 2019
                16 July 2019
                2019
                : 8
                : 118
                Affiliations
                [1 ]ISNI 0000 0001 2198 6209, GRID grid.411583.a, Department of Pharmaceutical Control, School of Pharmacy, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                [2 ]ISNI 0000 0001 2198 6209, GRID grid.411583.a, Department of Pharmacognosy, School of Pharmacy, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                [3 ]ISNI 0000 0001 2198 6209, GRID grid.411583.a, Biotechnology Research Center, Pharmaceutical Technology Institute, , Mashhad University of Medical Sciences, ; Mashhad, Iran
                Article
                559
                10.1186/s13756-019-0559-6
                6636059
                31346459
                662e5472-a6a7-4222-9847-b3beef2291e3
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 December 2018
                : 10 June 2019
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                antibiotic-resistant,antimicrobial activity,combination therapy,mechanism of action,natural products,phytochemicals

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