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      Bacterial Proteinaceous Compounds With Multiple Activities Toward Cancers and Microbial Infection

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          Abstract

          In recent decades, cancer and multidrug resistance have become a worldwide problem, resulting in high morbidity and mortality. Some infectious agents like Streptococcus pneumoniae, Stomatococcus mucilaginous, Staphylococcus spp. , E. coli. Klebsiella spp. , Pseudomonas aeruginosa, Candida spp., Helicobacter pylori, hepatitis B and C, and human papillomaviruses (HPV) have been associated with the development of cancer. Chemotherapy, radiotherapy and antibiotics are the conventional treatment for cancer and infectious disease. This treatment causes damage in healthy cells and tissues, and usually triggers systemic side-effects, as well as drug resistance. Therefore, the search for new treatments is urgent, in order to improve efficacy and also reduce side-effects. Proteins and peptides originating from bacteria can thus be a promising alternative to conventional treatments used nowadays against cancer and infectious disease. These molecules have demonstrated specific activity against cancer cells and bacterial infection; indeed, proteins and peptides can be considered as future antimicrobial and anticancer drugs. In this context, this review will focus on the desirable characteristics of proteins and peptides from bacterial sources that demonstrated activity against microbial infections and cancer, as well as their efficacy in vitro and in vivo.

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          Most cited references103

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          The expanding scope of antimicrobial peptide structures and their modes of action.

          Antimicrobial peptides (AMPs) are an integral part of the innate immune system that protect a host from invading pathogenic bacteria. To help overcome the problem of antimicrobial resistance, cationic AMPs are currently being considered as potential alternatives for antibiotics. Although extremely variable in length, amino acid composition and secondary structure, all peptides can adopt a distinct membrane-bound amphipathic conformation. Recent studies demonstrate that they achieve their antimicrobial activity by disrupting various key cellular processes. Some peptides can even use multiple mechanisms. Moreover, several intact proteins or protein fragments are now being shown to have inherent antimicrobial activity. A better understanding of the structure-activity relationships of AMPs is required to facilitate the rational design of novel antimicrobial agents. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Colicin biology.

            Colicins are proteins produced by and toxic for some strains of Escherichia coli. They are produced by strains of E. coli carrying a colicinogenic plasmid that bears the genetic determinants for colicin synthesis, immunity, and release. Insights gained into each fundamental aspect of their biology are presented: their synthesis, which is under SOS regulation; their release into the extracellular medium, which involves the colicin lysis protein; and their uptake mechanisms and modes of action. Colicins are organized into three domains, each one involved in a different step of the process of killing sensitive bacteria. The structures of some colicins are known at the atomic level and are discussed. Colicins exert their lethal action by first binding to specific receptors, which are outer membrane proteins used for the entry of specific nutrients. They are then translocated through the outer membrane and transit through the periplasm by either the Tol or the TonB system. The components of each system are known, and their implication in the functioning of the system is described. Colicins then reach their lethal target and act either by forming a voltage-dependent channel into the inner membrane or by using their endonuclease activity on DNA, rRNA, or tRNA. The mechanisms of inhibition by specific and cognate immunity proteins are presented. Finally, the use of colicins as laboratory or biotechnological tools and their mode of evolution are discussed.
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              Antibiotic-resistant bugs in the 21st century--a clinical super-challenge.

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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                06 August 2019
                2019
                : 10
                : 1690
                Affiliations
                [1] 1Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília , Brasília, Brazil
                [2] 2S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco , Campo Grande, Brazil
                [3] 3Pós-Graduação em Biologia Animal, Universidade de Brasilia , Brasília, Brazil
                Author notes

                Edited by: Bingyun Li, West Virginia University, United States

                Reviewed by: Ramya Viswanathan, National Institutes of Health (NIH), United States; Hai Liang, National Institutes of Health (NIH), United States

                *Correspondence: Octávio Luiz Franco, ocfranco@ 123456gmail.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2019.01690
                6691048
                31447795
                b3a0f1bf-2b68-4ff8-913e-38e297931db8
                Copyright © 2019 Rodrigues, Silva, Buccini, Duque, Dias and Franco.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 April 2019
                : 09 July 2019
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 118, Pages: 13, Words: 0
                Categories
                Microbiology
                Review

                Microbiology & Virology
                antimicrobial,anticancer,bacteriocin,protein,peptides
                Microbiology & Virology
                antimicrobial, anticancer, bacteriocin, protein, peptides

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