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      Special Issue: Shiga Toxin-Producing Escherichia coli

      editorial
      Microorganisms
      MDPI

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          Abstract

          Globally, Shiga toxin-producing Escherichia coli (STEC) is an important cause of diarrheal disease, most notably hemorrhagic colitis, and post-diarrheal sequela, such as hemolytic-uremic syndrome (HUS) [1]. Cattle are a major reservoir of STEC, with approximately half of the cases in humans attributable to foodborne exposure [2]. Prevention of human illness has mainly been through food safety measures [2]. Despite extensive research, no other generally accepted and effective preventive measures or therapies for STEC infections in human patients are available [3]. Many questions remain about STEC virulence factors, pathogenesis, detection, and other aspects that necessitate a continuation of basic and applied research on a wide front. This Special Issue includes 14 papers (nine articles, two communications, one review, one comment, and one reply) that collectively provide novel information on the epidemiology [4,5,6,7], virulence factors [7,8,9,10], and pathogenesis [11,12,13] of STEC, and the molecular structure or toxicity [14,15,16] and immunodetection [17] of Shiga toxin. A systematic review of STEC in Brazil found no data for 44% of the Brazilian states, highlighting the need for expansion of epidemiological monitoring to the entire country and alignment of food safety standards with that of international bodies [4,5,6]. Although STEC O111:H8 remains the leading serotype in Brazil, a diversity of other serotypes, some carrying virulence genes and belonging to specific sequence types, were isolated from human patients with bloody diarrhea and HUS, indicating the need for further studies to determine whether they have epidemiological relevance [7]. Several studies addressing virulence factors provided novel information about how they influence carriage in reservoir hosts and disease in human patients. A single base pair A to T transversion, intergenic to the curli divergent operons csgDEFG and csgBAC in E. coli O157:H7 stably conferred biofilm formation, epithelial cell invasion, and persistence in cattle [8]. E. coli O45:H2 is a close relative, phylogenetically, to E. coli O103:H2, sharing a high degree of homology in virulence factors, such as Stx prophages; however, it is distinct from E. coli O45:H16, suggesting that serotype O45:H2 may share virulence characteristics of O103:H2, which is frequently associated with severe illness [9]. E. coli O157:H7 secretes EF-Tu and L-asparaginase II, with the latter inhibiting T-lymphocyte proliferation [10]. OmpT contributes to E. coli O157:H7 adhesion to human epithelial cells [10]. Other studies, using a variety of methods and approaches, extend our knowledge of the pathogenesis of STEC infections. A comparison of the transcriptomic and phenotypic responses of host cells infected with STEC O113:H21 strains from a HUS patient or bovine feces having similar virulence factor profiles, found that the former induced greater and earlier host cell global gene expression with excessive inflammatory and apoptotic responses, which may explain its enhanced virulence [11]. A study reported on the identification of Stx2e receptors on porcine kidney epithelial cells, providing the first data on their Stx2e-mediated damage and suggesting a possible involvement in edema disease of swine [12]. Another study described the first report of E. coli O157:H7 causing attaching–effacing lesions in the uroepithelium and the first evidence of the utility of the gnotobiotic piglet as a model for studies of the pathogenesis of STEC-induced urinary tract infections [13]. Studies utilizing top-down proteomic analysis and a protocol for preparation of outer membrane vesicles (OMVs) provide further new information on Stx, and position scientists for future studies to address the effects of Stx on cells. Top-down proteomic analysis of the B-subunit successfully identified both Stx1a and Stx2a in STEC strains with results consistent with whole genome sequencing, validating the utility of this analytical method to distinguish types and subtypes of Stx [14]. A study structurally and functionally characterized Stx2k, a new subtype of Stx2, providing tools for early detection and control of STEC producing this less well-known toxin [15]. A protocol for the preparation of synthetic outer membrane vesicles (OMVs) with a defined lipid composition resembling the E. coli outer membrane and loading with functional Stx2a was described [16]. The OMVs were able to deliver Stx2a to host cells in the absence of other confounders of studies of Stx toxicity found in cell membranes—e.g., lipopolysaccharide. This work makes possible future studies on the degree of virulence associated with individual toxins from EHEC and other bacterial pathogens [16]. A study evaluating three immunological diagnostic assays for STEC (latex agglutination, lateral flow, and capture ELISA) found that all were highly sensitive and specific, indicating that robust tools for the diagnosis of STEC infections are available [17]. Collectively, the papers in this Special Issue on STEC reveal significant progress in the understanding of these pathogens, but they also highlight their complexity with the realization that more work is necessary to enable the development of more specific preventive measures and therapies.

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          Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis.

          Shiga toxin-producing Escherichia coli (STEC) are an important cause of foodborne disease, yet global estimates of disease burden do not exist. Our objective was to estimate the global annual number of illnesses due to pathogenic STEC, and resultant hemolytic uremic syndrome (HUS), end-stage renal disease (ESRD), and death.
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            Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2

            Shiga toxin (Stx) is the major virulence factor of Shiga toxin-producing Escherichia coli (STEC). Stx evolves rapidly and, as such, new subtypes continue to emerge that challenge the efficacy of existing disease management and surveillance strategies. A new subtype, Stx2k, was recently identified in E. coli isolated from a wide range of sources including diarrheal patients, animals, and raw meats, and was poorly detected by existing immunoassays. In this study, the structure of Stx2kE167Q was determined at 2.29 Å resolution and the conservation of structure with Stx2a was revealed. A novel polyclonal antibody capable of neutralizing Stx2k and an immunoassay, with a 10-fold increase in sensitivity compared to assays using extant antibodies, were developed. Stx2k is less toxic than Stx2a in Vero cell assays but is similar to Stx2a in receptor-binding preference, thermostability, and acid tolerance. Although Stx2k does not appear to be as potent as Stx2a to Vero cells, the wide distribution and blended virulence profiles of the Stx2k-producing strains suggest that horizontal gene transfer through Stx2k-converting phages could result in the emergence of new and highly virulent pathogens. This study provides useful information and tools for early detection and control of Stx2k-producing E. coli, which could reduce public risk of infection by less-known STECs.
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              Shiga-Toxin Producing Escherichia Coli in Brazil: A Systematic Review

              Shiga-toxin producing E. coli (STEC) can cause serious illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. This is the first systematic review of STEC in Brazil, and will report the main serogroups detected in animals, food products and foodborne diseases. Data were obtained from online databases accessed in January 2019. Papers were selected from each database using the Mesh term entries. Although no human disease outbreaks in Brazil related to STEC has been reported, the presence of several serogroups such as O157 and O111 has been verified in animals, food, and humans. Moreover, other serogroups monitored by international federal agencies and involved in outbreak cases worldwide were detected, and other unusual strains were involved in some isolated individual cases of foodborne disease, such as serotype O118:H16 and serogroup O165. The epidemiological data presented herein indicates the presence of several pathogenic serogroups, including O157:H7, O26, O103, and O111, which have been linked to disease outbreaks worldwide. As available data are concentrated in the Sao Paulo state and almost completely lacking in outlying regions, epidemiological monitoring in Brazil for STEC needs to be expanded and food safety standards for this pathogen should be aligned to that of the food safety standards of international bodies.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                22 December 2020
                January 2021
                : 9
                : 1
                : 1
                Affiliations
                School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0905, USA; rmoxley1@ 123456unl.edu
                Article
                microorganisms-09-00001
                10.3390/microorganisms9010001
                7821914
                33374893
                84ff153f-5101-4665-a699-31f963dfd374
                © 2020 by the author.

                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
                : 09 October 2020
                : 23 November 2020
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