Relevance of Bacteriophage 933W in the Development of Hemolytic Uremic Syndrome (HUS)

Cogliano, Manuel E. Del; Pinto, Alípio; Goldstein, Jorge; Zotta, Elsa; Ochoa, Federico; Fernández-Brando, Romina Jimena; Muniesa, Maite; Ghiringhelli, Pablo Daniel; Palermo, Marina S.; Bentancor, Leticia V.

doi:10.3389/fmicb.2018.03104

Cited by 18 publications

(14 citation statements)

References 26 publications

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“…For example, the Stx + phage Φ24 B is capable of increasing antibiotic resistance by reconfiguring the host metabolism [ 10 ]. In a mouse model, the introduction of Stx + phage 933W into a non-pathogenic E. coli strain is sufficient to produce highly lethal infection [ 11 ]. A greater number of DNA replication origins may help the Stx + phage P27 fine tune the lysogenic-lytic developmental decision in response to its microenvironment [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Modeling the Proteins from the exo-xis Region of Lambda and Shigatoxigenic Bacteriophages

Donaldson

2021

Antibiotics

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Despite decades of intensive research on bacteriophage lambda, a relatively uncharacterized region remains between the exo and xis genes. Collectively, exo-xis region genes are expressed during the earliest stages of the lytic developmental cycle and are capable of affecting the molecular events associated with the lysogenic-lytic developmental decision. In Shiga toxin-producing E. coli (STEC) and enterohemorragic E. coli (EHEC) that are responsible for food- and water-borne outbreaks throughout the world, there are distinct differences of exo-xis region genes from their counterparts in lambda phage. Together, these differences may help EHEC-specific phage and their bacterial hosts adapt to the complex environment within the human intestine. Only one exo-xis region protein, Ea8.5, has been solved to date. Here, I have used the AlphaFold and RoseTTAFold machine learning algorithms to predict the structures of six exo-xis region proteins from lambda and STEC/EHEC phages. Together, the models suggest possible roles for exo-xis region proteins in transcription and the regulation of RNA polymerase.

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Section: Introductionmentioning

confidence: 99%

Molecular Modeling the Proteins from the exo-xis Region of Lambda and Shigatoxigenic Bacteriophages

Donaldson

2021

Antibiotics

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“…However, low nucleotide sequence similarity (<70%) between these two phages was observed in several CDSs encoding the proteins, such as a few hypothetical proteins, integrase intA , and two phage anti-repressor protein Ant . Moreover, phage Stx2-converting phage Lys19259Vzw contained the stx2 gene and the regulatory genes associated with the production of Stx in bacteria, which were 100% identical in nucleotide sequence to their respective counterparts in the phage 933W, suggesting that Lys19259Vzw might have similar capabilities as the well-characterized phage 933W in contributing to the development of bacterial pathogenicity ( Del Cogliano et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Genomic Characterization of Two Shiga Toxin–Converting Bacteriophages Induced From Environmental Shiga Toxin–Producing Escherichia coli

et al. 2021

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Shiga toxin (Stx), encoded by stx genes located in prophage sequences, is the major agent responsible for the pathogenicity of Shiga toxin-producing Escherichia coli (STEC) and is closely associated with the development of hemolytic uremic syndrome (HUS). Although numerous Stx prophage sequences have been reported as part of STEC bacterial genomes, the information about the genomic characterization of Stx-converting bacteriophages induced from STEC strains is relatively scarce. The objectives of this study were to genomically characterize two Stx-converting phages induced from environmental STEC strains and to evaluate their correlations with published Stx-converting phages and STEC strains of different origins. The Stx1-converting phage Lys8385Vzw and the Stx2-converting phage Lys19259Vzw were induced from E. coli O103:H11 (RM8385) and E. coli O157:H7 (RM19259), respectively. Whole-genome sequencing of these phages was conducted on a MiSeq sequencer for genomic characterization. Phylogenetic analysis and comparative genomics were performed to determine the correlations between these two Stx-converting phages, 13 reference Stx-converting phages, and 10 reference STEC genomes carrying closely related Stx prophages. Both Stx-converting phages Lys8385Vzw and Lys19259Vzw had double-stranded DNA, with genome sizes of 50,953 and 61,072 bp, respectively. Approximately 40% of the annotated coding DNA sequences with the predicted functions were likely associated with the fitness for both phages and their bacterial hosts. The whole-genome–based phylogenetic analysis of these two Stx-converting phages and 13 reference Stx-converting phages revealed that the 15 Stx-converting phages were divided into three distinct clusters, and those from E. coli O157:H7, in particular, were distributed in each cluster, demonstrating the high genomic diversity of these Stx-converting phages. The genomes of Stx-converting phage Lys8385Vzw and Lys19259Vzw shared a high-nucleotide similarity with the prophage sequences of the selected STEC isolates from the clinical and environmental origin. The findings demonstrate the genomic diversity of Stx-converting phages induced from different STEC strains and provide valuable insights into the dissemination of stx genes among E. coli population via the lysogenization of Stx-converting phages.

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“…9). Induction efficiency of the Stx-phages is positively correlated to Stx-production [161][162][163][164][165][166], and widely used as a means to assess an STEC strains' individual Stx-conferred pathogenic potential (Fig. 9) [24,25,28,35,39,153,[167][168][169][170][171][172].…”

Section: Stx 2a -Production By St-820 and St-223 Complex Isolatesmentioning

confidence: 99%

Pathogenomes and variations in Shiga toxin production among geographically distinct clones of Escherichia coli O113:H21

et al. 2022

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Infections with globally disseminated Shiga toxin-producing Escherichia coli (STEC) of the O113:H21 serotype can progress to severe clinical complications, such as hemolytic uremic syndrome (HUS). Two phylogeographically distinct clonal complexes have been established by multi locus sequence typing (MLST). Infections with ST-820 isolates circulating exclusively in Australia have caused severe human disease, such as HUS. Conversely, ST-223 isolates prevalent in the US and outside Australia seem to rarely cause severe human disease but are frequent contaminants. Following a genomic epidemiology approach, we wanted to gain insights into the underlying cause for this disparity. We examined the plasticity in the genome make-up and Shiga toxin production in a collection of 20 ST-820 and ST-223 strains isolated from produce, the bovine reservoir, and clinical cases. STEC are notorious for assembly into fragmented draft sequences when using short-read sequencing technologies due to the extensive and partly homologous phage complement. The application of long-read technology (LRT) sequencing yielded closed reference chromosomes and plasmids for two representative ST-820 and ST-223 strains. The established high-resolution framework, based on whole genome alignments, single nucleotide polymorphism (SNP)-typing and MLST, includes the chromosomes and plasmids of other publicly available O113:H21 sequences and allowed us to refine the phylogeographical boundaries of ST-820 and ST-223 complex isolates and to further identify a historic non-shigatoxigenic strain from Mexico as a quasi-intermediate. Plasmid comparison revealed strong correlations between the strains’ featured pO113 plasmid genotypes and chromosomally inferred ST, which suggests coevolution of the chromosome and virulence plasmids. Our pathogenicity assessment revealed statistically significant differences in the Stx2a-production capabilities of ST-820 as compared to ST-223 strains under RecA-induced Stx phage mobilization, a condition that mimics Stx-phage induction. These observations suggest that ST-820 strains may confer an increased pathogenic potential in line with the strain-associated epidemiological metadata. Still, some of the tested ST-223 cultures sourced from contaminated produce or the bovine reservoir also produced Stx at levels comparable to those of ST-820 isolates, which calls for awareness and for continued surveillance of this lineage.

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Relevance of Bacteriophage 933W in the Development of Hemolytic Uremic Syndrome (HUS)

Cited by 18 publications

References 26 publications

Molecular Modeling the Proteins from the exo-xis Region of Lambda and Shigatoxigenic Bacteriophages

Molecular Modeling the Proteins from the exo-xis Region of Lambda and Shigatoxigenic Bacteriophages

Genomic Characterization of Two Shiga Toxin–Converting Bacteriophages Induced From Environmental Shiga Toxin–Producing Escherichia coli

Pathogenomes and variations in Shiga toxin production among geographically distinct clones of Escherichia coli O113:H21

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