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

Silje N Ramstad,Arne M Taxt,Umaer Naseer,Yngvild Wasteson,Jørgen V Bjørnholt,Lin T Brandal

doi:10.1016/j.micpath.2020.104636

Abstract

PurposeAntimicrobial treatment of Shiga toxin-producing Escherichia coli (STEC) infections is controversial because antimicrobials may stimulate Shiga toxin (Stx) production, and thereby increase the risk of developing haemolytic uremic syndrome (HUS). Previous in vitro studies have shown this mainly in infections caused by STEC serotype O157:H7. The aim of this study was to investigate induction of Stx transcription and production in different serotypes of STEC isolated from severely ill patients, following their exposure in vitro to six different classes of antimicrobials. MethodsWe investigated Stx transcription and production in 12 high-virulent STEC strains, all carrying the stx2a gene, of six different serotypes following their exposure to six classes of antimicrobials. Liquid cultures of the STEC strains were incubated with sub-inhibitory concentrations of the antimicrobials. We used reverse-transcription quantitative PCR to measure the relative expression of Stx2a mRNA and an enzyme-linked immunosorbent assay to quantify Stx production. ResultsIn general the antibiotics tested showed only minor effects on transcriptional levels of Stx2a. Ciprofloxacin caused an increase of Stx production in all but two strains, while gentamicin, meropenem and azithromycin did not induce Stx production in any of the STEC strains examined. STEC O104:H4 was the serotype that in greatest extent responded to antimicrobial exposure with an increase of stx2a transcription and Stx production. ConclusionGentamicin, meropenem and azithromycin exposure did not result in elevated Stx production. We recommend that this finding is investigated further in the search for candidates for future antimicrobial treatment of STEC.

Highlights

Infections caused by Shiga toxin-producing Escherichia coli (STEC) can cause a variety of gastrointestinal symptoms, including nausea, abdominal pain and mild to bloody diarrhoea, but may cause severe complications such as haemorrhagic colitis (HC), haemolytic uremic syndrome (HUS) and thrombotic microangiopathy [1,2,3]
Growth curves for each STEC strain, exposed and not exposed to antimicrobials, from two independent experiments are shown in Fig. S1
To address the dilemma of whether or not to administer antimicro bial treatment in severe STEC infections we investigated the effects of six different antimicrobials on stx2a transcription and Shiga toxins (Stx) production in 12 high-virulent STEC of various serotypes

Summary

Introduction

Infections caused by Shiga toxin-producing Escherichia coli (STEC) can cause a variety of gastrointestinal symptoms, including nausea, abdominal pain and mild to bloody diarrhoea, but may cause severe complications such as haemorrhagic colitis (HC), haemolytic uremic syndrome (HUS) and thrombotic microangiopathy [1,2,3]. HUS occurs in 5–15% of all STEC infections and mostly affects children [3]. In severe cases supportive therapy is required, but the role of antimicrobial treatment of STEC infections is controversial. Some clinical studies have indicated that antimicrobials can increase the risk of HUS development, and should be avoided [4,5]. The key virulence factors of STEC infection pathogenesis are Shiga toxins (Stx) and the ability to attach to the intestinal epithelium via the attaching and effacing mechanism.

Objectives

Methods

Results

Conclusion