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      The Herbal Compound Thymol Protects Mice From Lethal Infection by Salmonella Typhimurium

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          Abstract

          Type III secretion system (T3SS) is an essential pathogenic determinant for many important bacterial pathogens; it functions to thwart immune defense by delivering effectors into host cells. Because of its essential role in bacterial virulence, this machinery is an important target in the development of novel anti-virulence therapeutics. By using an effector-lactamase fusion reporter, we identified thymol, a monoterpene phenol derivative of cymene, as an effective inhibitor of the T3SS-1 of Salmonella Typhimurium. Our results indicate that thymol effectively protected mice against S. Typhimurium-induced mortality and pathological damages, suggesting that this compound can be developed for the control of infections caused by Salmonella species.

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          Most cited references21

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          Gut inflammation provides a respiratory electron acceptor for Salmonella

          Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation reacted with endogenous, luminal sulphur compounds (thiosulfate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to utilize tetrathionate as an electron acceptor produced a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus, the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen.
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            Salmonella interactions with host cells: type III secretion at work.

            J Galán (2000)
            The bacterial pathogen Salmonella enterica has evolved a very sophisticated functional interface with its vertebrate hosts. At the center of this interface is a specialized organelle, the type III secretion system, that directs the translocation of bacterial proteins into the host cell. Salmonella spp. encode two such systems that deliver a remarkable array of bacterial proteins capable of modulating a variety of cellular functions, including actin cytoskeleton dynamics, nuclear responses, and endocytic trafficking. Many of these bacterial proteins operate by faithful mimicry of host proteins, in some cases representing the result of extensive molecular tinkering and convergent evolution. The coordinated action of these type III secreted proteins secures the replication and survival of the bacteria avoiding overt damage to the host. The study of this remarkable pathogen is not only illuminating general paradigms in microbial pathogenesis but is also providing valuable insight into host cell functions.
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              Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents.

              Lippia gracilis Schauer (Verbenaceae) has long been recognized in folk medicine as a medicinal plant. The essential oil of Lippia gracilis has antimicrobial activity and is used externally to treat cutaneous diseases, burns, wounds, and ulcers. Recently, our research group demonstrated that the essential oil of Lippia gracilis leaves possesses antinociceptive and anti-inflammatory actions and its major component identified was thymol. The objective of this study was to assess the anti-inflammatory and wound healing activities of thymol in rodents.
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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
                16 May 2018
                2018
                : 9
                : 1022
                Affiliations
                [1] 1Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University , Changchun, China
                [2] 2Center of Infection and Immunity, The First Hospital, Jilin University , Changchun, China
                [3] 3Department of Biological Sciences, Purdue Institute for Inflammation, Immunology and Infectious Diseases and Purdue University , West Lafayette, IN, United States
                Author notes

                Edited by: Hui Wu, University of Alabama at Birmingham, United States

                Reviewed by: Yufeng Yao, Shanghai Jiao Tong University, China; Fernando Navarro-Garcia, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico

                *Correspondence: Zhao-Qing Luo luoz@ 123456purdue.edu

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                †These authors have contributed equally to this work.

                Article
                10.3389/fmicb.2018.01022
                5968388
                5750ca76-a811-4cc5-9566-20c372a9e13a
                Copyright © 2018 Zhang, Liu, Qiu, Luo and Deng.

                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 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
                : 16 February 2018
                : 30 April 2018
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 27, Pages: 7, Words: 5016
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 31620103918
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                type iii secretion,salmonella,anti-virulence,natural compounds,anti-inflammation

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