Effects of antimicrobials on Shiga toxin production in high-virulent Shiga toxin-producing Escherichia coli

Ramstad, Silje N.; Taxt, Arne M.; Naseer, Umaer; Wasteson, Yngvild; Bjørnholt, Jørgen Vildershøj; Brandal, Lin Thorstensen

doi:10.1016/j.micpath.2020.104636

Cited by 12 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first part of the NIPH2-Stx2a-phage (size 21.7 kbp) included the integrase gene and the stx2a gene, whereas the second part (size 23.5 kbp) contained the integration site yciD and structural genes, together with a shadow phage, almost identical to the shadow phage present in the NIPH1 strain. We know from previous studies that NIPH2 did produce Stx and lysed, but if, or how, this affects the creation and assembly of the Stx2a phage body of this strain is not known ( Ramstad et al, 2020 ). The organization of this Stx2a phage within the STEC genome might be due to the frequent recombination observed in E. coli ( Fitzgerald et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Characterization of Shiga Toxin 2a Encoding Bacteriophages Isolated From High-Virulent O145:H25 Shiga Toxin-Producing Escherichia coli

et al. 2021

Self Cite

View full text Add to dashboard Cite

Shiga toxin-producing Escherichia coli (STEC) may cause severe disease mainly due to the ability to produce Shiga toxins (Stx) encoded on bacteriophages. In Norway, more than 30% of the reported cases with STEC O145:H25 develop hemolytic uremic syndrome (HUS), and most cases, with known travel history, acquired the infection domestically. To describe phage characteristics associated with high virulence, we extracted the Stx2a phage sequences from eight clinical Norwegian O145:H25 STEC to conduct in-depth molecular characterization using long and short read sequencing. The Stx2a phages were annotated, characterized, and compared with previously published Stx2a phages isolated from STEC of different serotypes. The Norwegian O145:H25 Stx2a phages showed high sequence identity (>99%) with 100% coverage. The Stx2a phages were located at the integration site yciD, were approximately 45 kbp long, and harbored several virulence-associated genes, in addition to stx2a, such as nanS and nleC. We observed high sequence identity (>98%) and coverage (≥94%) between Norwegian O145:H25 Stx2a phages and publicly available Stx2a phages from O145:H25 and O145:H28 STEC, isolated from HUS cases in the USA and a hemorrhagic diarrhea case from Japan, respectively. However, low similarity was seen when comparing the Norwegian O145:H25 Stx2a phage to Stx2a phages from STEC of other serotypes. In all the Norwegian O145:H25 STEC, we identified a second phage or remnants of a phage (a shadow phage, 61 kbp) inserted at the same integration site as the Stx2a phage. The shadow phage shared similarity with the Stx2a phage, but lacked stx2a and harbored effector genes not present in the Stx2a phage. We identified a conserved Stx2a phage among the Norwegian O145:H25 STEC that shared integration site with a shadow phage in all isolates. Both phage and shadow phage harbored several virulence-associated genes that may contribute to the increased pathogenicity of O145:H25 STEC.

show abstract

Section: Resultsmentioning

confidence: 99%

Characterization of Shiga Toxin 2a Encoding Bacteriophages Isolated From High-Virulent O145:H25 Shiga Toxin-Producing Escherichia coli

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The prevalence of azithromycin (macrolide) resistance among the high-virulent strains was low (2.4%) and azithromycin may represent an empiric treatment alternative. Ciprofloxacin could also be effective against most high-virulent STEC and has shown positive treatment outcomes in some clinical studies, however many in vitro studies have shown a high Stx induction potential of ciprofloxacin [8,9,14,16]. Antimicrobial susceptibility testing of strains before initiating antimicrobial treatment is preferable, however for severe infections urgency dictates empirical treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Azithromycin, ciprofloxacin and fosfomycin (alone or in combination) are among the antimicrobials that have shown promising results in the treatment of severe STEC infections [8,9,[11][12][13]. However, ciprofloxacin has shown to trigger Stx production in vitro [14][15][16]. Also, several in vitro studies investigating antimicrobials and their effects on Stx production have demonstrated that azithromycin, gentamicin and meropenem are potential candidates for treatment [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of genotypic antimicrobial resistance in clinical Shiga toxin-producing Escherichia coli in Norway, 2018 to 2020

Ramstad

Brandal

Taxt

et al. 2021

Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

Introduction. Shiga toxin-producing Escherichia coli (STEC) can cause severe to fatal disease in humans. Antimicrobial treatment is sometimes necessary, but contraindicated due to undesirable clinical outcome. However, recent studies have shown promising outcomes following antimicrobial treatment. Before the establishment of a possible antimicrobial treatment strategy for STEC infections, the prevalence of antimicrobial resistance in STEC needs to be determined. Gap Statement. The resistance status of Norwegian clinical STEC is not known and should be assessed. Aim. We aim to characterize genotypic antimicrobial resistance determinants in clinical STEC in Norway, and determine the prevalence of genotypic resistance in order to inform possible antimicrobial treatment options for STEC infections. Methodology. We included all clinical STEC submitted to the Norwegian Reference Laboratory from March 2018 to April 2020. All samples were whole-genome sequenced and screened for genotypic antimicrobial resistance,virulence determinants and plasmid incompatibility groups. We performed phylogenetic clustering of STEC by core-genome multi-locus sequence typing, and statistical association analyses between isolate characteristics and genotypic resistance. Results. A total of 459 STEC were analysed. For 385 (83.9 %) STEC we did not identify any antimicrobial resistance determinants. Seventy-four STEC (16.1 %) harboured antimicrobial resistance determinants against one or more antimicrobial classes. The most frequent genotypic resistance was identified against aminoglycosides (10.5 %). Thirty-nine STEC (8.5 %) had a multi-drug resistance (MDR) genotype. Genotypic resistance was more prevalent in non-O157 than O157 STEC (P=0.02). A positive association was seen between genotypic resistance and the low-virulent STEC O117:H7 phylogenetic cluster (no. 14) (P<0.001). Genotypic resistance was not significantly associated to high-virulent STEC. STEC O146:H28 and isolates harbouring the plasmid replicon type IncQ1 were positively associated with MDR. Conclusion. The overall prevalence of genotypic resistance in clinical STEC in Norway is low (16.1 %). Genotypic resistance is more prevalent in non-O157 strains compared to O157 strains, and not significantly associated to high-virulent STEC. Resistance to antimicrobials suggested for treatment, especially azithromycin is low and may present an empiric treatment alternative for severe STEC infections.

show abstract

“…Stxs are encoded by genes located on genomes of lambdoid prophages and certain antibiotics stimulate their induction leading to enhanced production of Stxs [288]. Although numerous studies have reported that antibiotics enhance the severity of disease symptoms and increase the risk of progression to HUS development, further corroborated by in vitro antibiotic studies using certain EHEC strains, others have reported that antibiotics do not have any effect or can even reduce the rate of HUS development in EHEC infections [289][290][291][292][293][294][295][296]. The current data situation leads to the conclusion that the infecting EHEC strain, the type of antibiotic, and the timing of its application appear to significantly affect the development of HUS in EHEC-infected patients [285].…”

Section: Application Of Antibiotics or Not That's The Questionmentioning

confidence: 99%

Enterohemorrhagic Escherichia coli and a Fresh View on Shiga Toxin-Binding Glycosphingolipids of Primary Human Kidney and Colon Epithelial Cells and Their Toxin Susceptibility

Detzner

Pohlentz

Müthing

2022

IJMS

View full text Add to dashboard Cite

Enterohemorrhagic Escherichia coli (EHEC) are the human pathogenic subset of Shiga toxin (Stx)-producing E. coli (STEC). EHEC are responsible for severe colon infections associated with life-threatening extraintestinal complications such as the hemolytic-uremic syndrome (HUS) and neurological disturbances. Endothelial cells in various human organs are renowned targets of Stx, whereas the role of epithelial cells of colon and kidneys in the infection process has been and is still a matter of debate. This review shortly addresses the clinical impact of EHEC infections, novel aspects of vesicular package of Stx in the intestine and the blood stream as well as Stx-mediated extraintestinal complications and therapeutic options. Here follows a compilation of the Stx-binding glycosphingolipids (GSLs), globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) and their various lipoforms present in primary human kidney and colon epithelial cells and their distribution in lipid raft-analog membrane preparations. The last issues are the high and extremely low susceptibility of primary renal and colonic epithelial cells, respectively, suggesting a large resilience of the intestinal epithelium against the human-pathogenic Stx1a- and Stx2a-subtypes due to the low content of the high-affinity Stx-receptor Gb3Cer in colon epithelial cells. The review closes with a brief outlook on future challenges of Stx research.

show abstract

Effects of antimicrobials on Shiga toxin production in high-virulent Shiga toxin-producing Escherichia coli

Cited by 12 publications

References 39 publications

Characterization of Shiga Toxin 2a Encoding Bacteriophages Isolated From High-Virulent O145:H25 Shiga Toxin-Producing Escherichia coli

Characterization of Shiga Toxin 2a Encoding Bacteriophages Isolated From High-Virulent O145:H25 Shiga Toxin-Producing Escherichia coli

Prevalence of genotypic antimicrobial resistance in clinical Shiga toxin-producing Escherichia coli in Norway, 2018 to 2020

Enterohemorrhagic Escherichia coli and a Fresh View on Shiga Toxin-Binding Glycosphingolipids of Primary Human Kidney and Colon Epithelial Cells and Their Toxin Susceptibility

Contact Info

Product

Resources

About