Special Issue "Shiga Toxin: Occurrence, Pathogenicity, Detection and Therapies"
A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".
Deadline for manuscript submissions: 31 December 2021.
Special Issue Editor
Interests: Shiga-toxin-producing Escherichia coli (STEC) ; (i) STEC interactions with the bovine gastrointestinal cells, especially those at the recto-anal junction (RAJ); (ii) STEC factors that promote its survival in the bovine rumen and persistence at the RAJ; (iii) Adherence mechanisms deployed by STEC in strain- and host-dependent manner; (iv) Development of rational subunit vaccines and vaccine alternatives that target STEC in cattle; and (v) Development of diagnostic assays to study STEC adherence and to identify STEC-colonized cattle.
Special Issue Information
Shiga-toxin-producing Escherichia coli (STEC) are the third leading cause of foodborne illness after Campylobacter and Salmonella, and are implicated in 265,000 illnesses in the US and 2.8M infections globally. Significant economic losses incurred by public health, agriculture and the meat industry estimated at $993 million per year prompted the declaration of commonly implicated STEC serotypes (O157, O26, O103, O111, O121, O145, and O45) as food adulterants by the USDA Food Safety and Inspection Service. STEC infections are acquired through the ingestion of bacteria-contaminated food or water, or by hand-to-mouth transmission. Cattle are considered to be the primary STEC reservoirs, as most outbreaks are directly or indirectly associated with cattle. Following infection, some individuals remain asymptomatic, while others develop watery or bloody diarrhea that may progress to fatal secondary sequelae. Successful infection is established following the ingestion of only a few organisms (50–500 viable bacteria), attributable to multiple-acid tolerance and quorum sensing mechanisms. Virulence factors such as the phage-encoded Shiga toxins (Stx), plasmid-encoded hemolysin, and various adherence factors including intimin, encoded by the eae gene on the pathogenicity-island locus of enterocyte effacement (LEE), play a significant role in human disease. Cattle remain asymptomatic due to the absence of receptors for Stx; without uptake of toxin there is no resulting systemic failure as observed in humans. Thus, Stx are the primary virulence factors contributing towards STEC pathogenicity in humans through niche establishment, nutrient acquisition, host immune response modulation/evasion, and targeted cell pathology.
In this Special Issue, we seek to provide a comprehensive collection of publications on Stx in the context of: (i) toxin structure, acquisition, evolution, variants, and mode of action; (ii) host–pathogen interaction—structural and immune; (iii) disease prediction and risk assessment; and (iv) toxin detection and targeted therapies. Review and research papers describing established and novel concepts are welcome.
Dr. Indira Kudva
Guest Editor
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
Keywords
- E. coli
- STEC
- Shiga toxin
- toxicity
- variants
- pathogenicity
- disease
- risk
- detection
- therapy
Planned Papers
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: AB5 Enterotoxins and Pathogenesis: Perspectives gleaned from studies of Shiga toxins
Authors: Erika N. Biernbaum1, 2 and Indira T. Kudva2
Affiliation: 1 Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee. 2 Food Safety Enteric Pathogens Research Unit, National Animal Disease Center/USDA, Ames, Iowa.
Abstract: Foodborne illnesses affect 600 million people worldwide annually, with several of the bacterial agents of infection belonging to the Enterobacteriaceae family. Many of these pathogens secrete AB5 toxins, such as ArtAB, EcPlt, LT-I, SubAB, and Shiga toxins, to elicit infection in humans. In this review we are providing a synopsis on the mechanisms of action and pathogenesis of AB5 toxins expressed by Salmonella, Shigella, and Escherichia coli, along with landmark virulence factors for Campylobacter and Yersinia species. Subsequently, we are presenting a brief overview of Shiga toxins, Shiga toxin-producing E. coli (STEC) disease, detection methodologies, and available treatment options.
Title: Mutation of the Shiga toxin type 1a B subunit in the context of a chimeric holotoxoid or by itself eliminates the capacity to induce a neutralizing response in mice
Authors: Roberto J. Cieza1, Joshua C. Bunger1, Lisa M. Russo1,2, Beth A. McNichol1, and Angela R. Melton-Celsa2,*
Affiliation:
1Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD 20817 USA
2Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 USA
Abstract: Infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) can result in bloody diarrhea with possible progression to hemolytic uremic syndrome (HUS). STEC may encode Stx1a and/or Stx2a, two biologically similar, but antigenically distinct, toxins. We previously showed that vaccination of mice with a chimeric Stx toxoid composed of an inactivated A-subunit from Stx2a and a functional Stx1a B-subunit elicited neutralizing and protective antibodies against both Stx1a and Stx2a. The purpose of this study was to develop and test a chimeric toxoid in which both toxin subunits domains were non-functional. We found that the when both the Stx2a A subunit and the Stx1a B subunits were genetically toxoided that we did not recover a holotoxoid. Therefore, we tested bacterial lysates that encoded the chimeric toxoid construct for the capacity to elicit an immune response. We found that although immunization with the lysate induced an immune response to both Stx2a and Stx1a, sera from the vaccinated mice did not neutralize either toxin on Vero cells. We next asked if immunization with just the Stx2a A-subunit or the toxoided A-subunit could elicit an IgG response or neutralizing response from the mice. We found that although sera from mice given either the intact or toxoided A-subunit generated an anti-Stx2a IgG response, that only the sera from mice given the intact A-subunit neutralized Stx2a for Vero cells. Next, we explored the potential of the toxoided Stx1a B-subunit toxoids to elicit an Stx-neutralizing response. We found that immunization with Stx1a B-subunit, but not Stx1a B-subunit with either a D17H or G60D mutation elicited an Stx1a-neutralizing response, though both B subunit toxoids did cause the mice to mount an IgG response to Stx1a. Taken together, we found that mutation of the Stx1a B-subunit, but not the Stx2a A-subunit prevented the generation of a toxin-neutralizing antibody response in mice.