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      Recent Advances in Shiga Toxin-Producing Escherichia coli Research in Latin America

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          Abstract

          Pathogenic Escherichia coli are known to be a common cause of diarrheal disease and a frequently occurring bacterial infection in children and adults in Latin America. Despite the effort to combat diarrheal infections, the south of the American continent remains a hot spot for infections and sequelae associated with the acquisition of one category of pathogenic E. coli, the Shiga toxin-producing E. coli (STEC). This review will focus on an overview of the prevalence of different STEC serotypes in human, animals and food products, focusing on recent reports from Latin America outlining the recent research progress achieved in this region to combat disease and endemicity in affected countries and to improve understanding on emerging serotypes and their virulence factors. Furthermore, this review will highlight the progress done in vaccine development and treatment and will also discuss the effort of the Latin American investigators to respond to the thread of STEC infections by establishing a multidisciplinary network of experts that are addressing STEC-associated animal, human and environmental health issues, while trying to reduce human disease. Regardless of the significant scientific contributions to understand and combat STEC infections worldwide, many significant challenges still exist and this review has focus in the Latin American efforts as an example of what can be accomplished when multiple groups have a common goal.

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          CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells.

          CD40 ligand (CD40L, CD154), a transmembrane protein structurally related to the cytokine TNF-alpha, was originally identified on stimulated CD4+ T cells, and later on stimulated mast cells and basophils. Interaction of CD40L on T cells with CD40 on B cells is of paramount importance for the development and function of the humoral immune system. CD40 is not only constitutively present on B cells, but it is also found on monocytes, macrophages and endothelial cells, suggesting that CD40L has a broader function in vivo. We now report that platelets express CD40L within seconds of activation in vitro and in the process of thrombus formation in vivo. Like TNF-alpha and interleukin-1, CD40L on platelets induces endothelial cells to secrete chemokines and to express adhesion molecules, thereby generating signals for the recruitment and extravasation of leukocytes at the site of injury. Our results indicate that platelets are not only involved in haemostasis but that they also directly initiate an inflammatory response of the vessel wall.
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            Shiga toxins and stx phages: highly diverse entities.

            Shiga toxins are the main virulence factors of a group of Escherichia coli strains [Shiga toxin-producing E. coli (STEC)] that cause severe human diseases, such as haemorrhagic colitis and haemolytic-uraemic syndrome. The Shiga toxin family comprises several toxin subtypes, which have been differentially related to clinical manifestations. In addition, the phages that carry the Shiga toxin genes (stx phages) are also diverse. These phages play an important role not only in the dissemination of Shiga toxin genes and the emergence of new STEC strains, but also in the regulation of Shiga toxin production. Consequently, differences in stx phages may affect the dissemination of stx genes as well as the virulence of STEC strains. In addition to presenting an overview of Shiga toxins and stx phages, in this review we highlight current knowledge about the diversity of stx phages, with emphasis on its impact on STEC virulence. We consider that this diversity should be taken into account when developing STEC infection treatments and diagnostic approaches, and when conducting STEC control in reservoirs.
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              Mouse Models of Escherichia coli O157:H7 Infection and Shiga Toxin Injection

              Escherichia coli O157:H7 has been responsible for multiple food- and waterborne outbreaks of diarrhea and/or hemorrhagic colitis (HC) worldwide. More importantly, a portion of E. coli O157:H7-infected individuals, particularly young children, develop a life-threatening sequela of infection called hemolytic uremic syndrome (HUS). Shiga toxin (Stx), a potent cytotoxin, is the major virulence factor linked to the presentation of both HC and HUS. Currently, treatment of E. coli O157:H7 and other Stx-producing E. coli (STEC) infections is limited to supportive care. To facilitate development of therapeutic strategies and vaccines for humans against these agents, animal models that mimic one or more aspect of STEC infection and disease are needed. In this paper, we focus on the characteristics of various mouse models that have been developed and that can be used to monitor STEC colonization, disease, pathology, or combinations of these features as well as the impact of Stx alone.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                28 September 2018
                December 2018
                : 6
                : 4
                : 100
                Affiliations
                [1 ]Department of Microbiology and Immunology, Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
                [2 ]Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina; mmamaral74@ 123456gmail.com
                [3 ]Laboratory of Genetic Engineering and Molecular Biology, Institute of Basic and Applied Microbiology, National University of Quilmes, Bernal, Buenos Aires 1876, Argentina; lbentan@ 123456unq.edu.ar
                [4 ]Instituto de Genética Veterinaria Ing. Fernando N. Dulout (UNLP-CONICET, La Plata), Facultad de Ciencias Veterinarias, La Plata 1900, Argentina; lgalli@ 123456igevet.gob.ar
                [5 ]Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Fisiología y Biofísica Houssay, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina; jogol@ 123456fmed.uba.ar
                [6 ]Centro de Investigación Veterinaria de Tandil (CONICET-CIC-UNCPBA), Facultad de Ciencias Veterinarias, Tandil 7000, Argentina; akruger@ 123456vet.unicen.edu.ar
                [7 ]Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; maricarmen.rojaslopez@ 123456gmail.com
                Author notes
                [* ]Correspondence: altorres@ 123456utmb.edu ; Tel.: +1-409-747-0189
                Author information
                https://orcid.org/0000-0001-6450-0643
                Article
                microorganisms-06-00100
                10.3390/microorganisms6040100
                6313304
                30274180
                1a1dafef-6d2c-4c5b-8b0a-548fd63fcccf
                © 2018 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
                : 06 August 2018
                : 28 September 2018
                Categories
                Review

                shiga toxin,stec,shiga toxin-producing e. coli,enterohemorrhagic e. coli,hemolytic uremic syndrome,diarrhea,vaccines,therapeutics,phages

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