The Probiotic Escherichia coli Strain Nissle 1917 Combats Lambdoid Bacteriophages stx and λ.

Susanne Bury,Rudolf Von Bünau,Tobias A Oelschlaeger,Manonmani Soundararajan,Konrad U Förstner,Richa Bharti

doi:10.3389/fmicb.2018.00929

Susanne Bury, Rudolf Von Bünau + Show 4 more

Open Access

https://doi.org/10.3389/fmicb.2018.00929

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Abstract

Shiga toxin (Stx) producing E. coli (STEC) such as Enterohemorrhagic E. coli (EHEC) are the major cause of foodborne illness in humans. In vitro studies showed the probiotic Escherichia coli strain Nissle 1917 (EcN) to efficiently inhibit the production of Stx. Life threatening EHEC strains as for example the serotype O104:H4, responsible for the great outbreak in 2011 in Germany, evolutionary developed from certain E. coli strains which got infected by stx2-encoding lambdoid phages turning the E. coli into lysogenic and subsequently Stx producing strains. Since antibiotics induce stx genes and Stx production, EHEC infected persons are not recommended to be treated with antibiotics. Therefore, EcN might be an alternative medication. However, because even commensal E. coli strains might be converted into Stx-producers after becoming host to a stx encoding prophage, we tested EcN for stx-phage genome integration. Our experiments revealed the resistance of EcN toward not only stx-phages but also against lambda-phages. This resistance was not based on the lack of or by mutated phage receptors. Rather it involved the expression of a phage repressor (pr) gene of a defective prophage in EcN which was able to partially protect E. coli K-12 strain MG1655 against stx and lambda phage infection. Furthermore, we observed EcN to inactivate phages and thereby to protect E. coli K-12 strains against infection by stx- as well as lambda-phages. Inactivation of lambda-phages was due to binding of lambda-phages to LamB of EcN whereas inactivation of stx-phages was caused by a thermostable protein of EcN. These properties together with its ability to inhibit Stx production make EcN a good candidate for the prevention of illness caused by EHEC and probably for the treatment of already infected people.

Highlights

Foodborne illness caused by enteropathogenic bacteria are a great concern on population health
It is of clinical importance that Escherichia coli strain Nissle 1917 (EcN) is not getting infected by stxphages to be able to use it as a probiotic drug treatment during an Enterohemorrhagic E. coli (EHEC) infection or as a preventive medication
To identify if EcN undergoes lysogenic infection, it was incubated with stx-phages from the STEC strain EDL933 and lambda-phages from the K-12 strain 993 as described in section Lysogeny Detection to allow the phage integration into bacterial genome

Summary

Introduction

Foodborne illness caused by enteropathogenic bacteria are a great concern on population health. Among those the hemolytic uremic syndrome and bloody diarrhea are symptoms caused by foodborne pathogenic Escherichia coli (E. coli) strains, the so-called STEC strains (Conway, 2015). EcN Combats Lambdoid Phages is a toxic protein which is closely related to the Stx from the gramnegative bacterium Shigella dysenteriae (Fraser et al, 2004). Research on the mode of action of Stx revealed that the two component AB5 toxin binds to the globotriaosylceramide (Gb3) receptor of eukaryotic cells and blocks protein synthesis due to ribosome inactivation by the subunit A, which results in cell death by apoptosis (Tesh, 2012; Melton-Celsa, 2014)

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