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Microorganisms
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Shiga Toxin-Producing Escherichia coli: Diagnostics, Characterization, and Pathogenesis
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Shiga Toxin-Producing Escherichia coli: Diagnostics, Characterization, and Pathogenesis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (15 March 2025) | Viewed by 2255

Special Issue Editor

Dr. Xiangning Bai

E-Mail Website
Guest Editor
1. Department of Microbiology, Division of Laboratory Medicine, Oslo University Hospital, 0372 Oslo, Norway
2. Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden
3. Department of Clinical Microbiology, Division of Laboratory Medicine, Karolinska Institutet, 141 52 Stockholm, Sweden
Interests: Shiga toxin-producing Escherichia coli; pathogenesis; genomics and metagenomics; microbiome; infectious diseases

Special Issue Information

Dear Colleagues,

Shiga toxin-producing Escherichia coli (STEC), representing a genetically and phenotypically diverse group of E. coli strains characterized by the production of one or more Shiga toxins (Stxs), has been linked to a broad spectrum of clinical outcomes ranging from asymptomatic infection, bloody diarrhea, and the potentially life-threatening complication known as hemolytic uremic syndrome (HUS). The Stx is the key virulence factor of STEC and comprises two types: Stx1 and Stx2. The most predominant STEC serotype, O157:H7, normally producing the Stx2a subtype (with or without Stx2c), has been strongly associated with severe clinical symptoms, such as HUS. In recent years, non-O157 STEC infections are increasingly recognized as the main cause of sporadic cases or outbreaks worldwide, primarily due to improvements in diagnostics. To date, there is no curative treatment for STEC-HUS, and patient care largely remains supportive. Antibiotic therapy is considered to be contraindicated, as it boosts the release of Stxs and stimulates the absorption of the toxin, which ultimately increases the risk of HUS. Recent studies show that there are no single or combination of bacterial genetic markers that can predict the potential of STEC strains to cause severe clinical outcomes, evidencing that various bacterial and host-related factors, e.g., variations in host immunity, contribute to STEC pathogenicity and HUS progression.

The aim of this Special Issue is to summarize the current knowledge and report up-to-date research on the diagnostics, characterization, and pathogenesis of STEC, which may shed light upon new perspectives for the management of STEC-associated diseases, in particular HUS and its complications.

Dr. Xiangning Bai
Guest Editor

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Keywords

  • Shiga toxin-producing Escherichia coli
  • diagnostics
  • characterization
  • pathogenetic mechanism
  • virulence
  • disease severity
  • diarrhea
  • hemolytic uremic syndrome
  • bacteria-host interactions

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Published Papers (3 papers)

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Research

7 pages, 374 KiB  
Communication
Occurrence of Multiple stx1 Genes and Rare Genomic Variation in stx1 Shiga Toxin-Producing Escherichia coli
by Michaela Projahn, Maria Borowiak, Matthias Contzen, Ekkehard Hiller, Christiane Werckenthin, Elisabeth Schuh and Carlus Deneke
Microorganisms 2025, 13(5), 1079; https://doi.org/10.3390/microorganisms13051079 - 6 May 2025
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Abstract
Shiga toxin-producing Escherichia coli are important foodborne pathogens. There are several subtypes of the Shiga toxin Stx known, with Stx2 (a–o) being more diverse than Stx1 (a, c, d). Multiple occurrences of stx2 genes as well as combinations of stx1 and stx2 have [...] Read more.
Shiga toxin-producing Escherichia coli are important foodborne pathogens. There are several subtypes of the Shiga toxin Stx known, with Stx2 (a–o) being more diverse than Stx1 (a, c, d). Multiple occurrences of stx2 genes as well as combinations of stx1 and stx2 have been reported. However, there is a lack of knowledge on the occurrence of multiple stx1 genes in STEC strains. Here, we report two strains from food and animal feces which show genomic variations in the stx1 operon. The first strain harbors stx1a and stx1c genes, and the second strain shows an inactive stx1 operon due to an insertion in the stxA1a subunit gene. The screening of publicly available complete genome sequences of STEC revealed further strains harboring multiple stx1 genes, indicating that those strains also occur in human infections. This should be kept in mind when applying routine diagnostic methods like PCR, that do not detect multiple occurrences of stx1 genes of the same subtype. Moreover, the impact on the severity of human infections due to multiple stx1 genes has not been investigated well. Full article
(This article belongs to the Special Issue Shiga Toxin-Producing Escherichia coli: Diagnostics, Characterization, and Pathogenesis)
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15 pages, 1948 KiB  
Article
Characterization of Seven Shiga Toxin Phages Induced from Human-Derived Shiga Toxin-Producing Escherichia coli
by Xinxia Sui, Shuyun Wang, Xi Yang, Peihua Zhang, Hui Sun, Xiangning Bai and Yanwen Xiong
Microorganisms 2025, 13(4), 783; https://doi.org/10.3390/microorganisms13040783 - 28 Mar 2025
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Abstract
Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause asymptomatic infections, diarrhea, hemorrhagic colitis (HC), and life-threatening hemolytic uremic syndrome (HUS) in humans. Shiga toxins (Stxs) are the major virulence factors encoded by prophages, which play a crucial role in STEC [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause asymptomatic infections, diarrhea, hemorrhagic colitis (HC), and life-threatening hemolytic uremic syndrome (HUS) in humans. Shiga toxins (Stxs) are the major virulence factors encoded by prophages, which play a crucial role in STEC pathogenesis and evolution. In this study, seven Stx phages were obtained from STEC isolates derived from four asymptomatic food handlers, two diarrheal patients, and one outbreak-related HUS case in China. These phages exhibited three morphologies: an icosahedral head with either a short or a long tail, and an elongated head with a long tail. Of these seven phages, three were sequenced; two showed a complete identity with their respective prophage sequences, while phage phiXuzhou21-Stx2a lacked a 6011 bp region-encoding integrase, excisionase, and hypothetical proteins. Comparative genome analysis revealed that the induced seven phages primarily varied in their regulatory regions, whereas the short-tailed phages showed high similarity in their morphogenesis-related regions. In addition, five of the seven phages demonstrated the ability to convert non-pathogenic E. coli strains into Stx-producing transduced strains. Under inducing conditions, Stx expression levels were significantly increased in these transduced strains. These findings underscore the diversity and adaptability of Stx phages and emphasize the importance of understanding their genetic and molecular interactions with host bacteria. Full article
(This article belongs to the Special Issue Shiga Toxin-Producing Escherichia coli: Diagnostics, Characterization, and Pathogenesis)
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16 pages, 3744 KiB  
Article
Molecular Evolutionary Analyses of Shiga toxin type 2 subunit A Gene in the Enterohemorrhagic Escherichia coli (EHEC)
by Ryusuke Kimura, Hirokazu Kimura, Tatsuya Shirai, Yuriko Hayashi, Yuka Sato-Fujimoto, Wataru Kamitani, Akihide Ryo and Haruyoshi Tomita
Microorganisms 2024, 12(9), 1812; https://doi.org/10.3390/microorganisms12091812 - 2 Sep 2024
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Abstract
To better understand the molecular genetics of the Shiga toxin type 2 subunit A gene (stx2A gene), we collected many subtypes of stx2A genes and performed detailed molecular evolutionary analyses of the gene. To achieve the aim of the study, we used [...] Read more.
To better understand the molecular genetics of the Shiga toxin type 2 subunit A gene (stx2A gene), we collected many subtypes of stx2A genes and performed detailed molecular evolutionary analyses of the gene. To achieve the aim of the study, we used several bioinformatics technologies, including time-scaled phylogenetic analyses, phylogenetic distance analyses, phylodynamics analyses, selective pressure analyses, and conformational epitope analyses. A time-scaled phylogeny showed that the common ancestor of the stx2A gene dated back to around 18,600 years ago. After that, the gene diverged into two major lineages (Lineage 1 and 2). Lineage 1 comprised the stx2a–2d subtypes, while Lineage 2 comprised the stx2e, 2g, 2h, and 2o subtypes. The evolutionary rates of the genes were relatively fast. Phylogenetic distances showed that the Lineage 2 strains had a wider genetic divergence than Lineage 1. Phylodynamics also indicated that the population size of the stx2A gene increased after the 1930s and spread globally. Moreover, negative selection sites were identified in the Stx2A proteins, and these sites were diffusely distributed throughout the protein. Two negative selection sites were located adjacent to an active site of the common Stx2A protein. Many conformational epitopes were also estimated in these proteins, while no conformational epitope was found adjacent to the active site. The results suggest that the stx2A gene has uniquely evolved and diverged over an extremely long time, resulting in many subtypes. The dominance of the strains belonging to Lineage 1 suggests that differences in virulence may be involved in the prosperity of the offspring. Furthermore, some subtypes of Stx2A proteins may be able to induce effective neutralizing antibodies against the proteins in humans. Full article
(This article belongs to the Special Issue Shiga Toxin-Producing Escherichia coli: Diagnostics, Characterization, and Pathogenesis)
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