Genomic Insights Into Clinical Shiga Toxin-Producing Escherichia coli Strains: A 15-Year Period Survey in Jönköping, Sweden

Xiangning Bai; Ji Zhang; Ying Hua; Cecilia Jernberg; Yanwen Xiong; Nigel French; Sture Löfgren; Ingela Hedenström; Anoop Ambikan; Sara Mernelius; Andreas Matussek

doi:10.3389/fmicb.2021.627861

Genomic Insights Into Clinical Shiga Toxin-Producing Escherichia coli Strains: A 15-Year Period Survey in Jönköping, Sweden

Front Microbiol. 2021 Feb 5:12:627861. doi: 10.3389/fmicb.2021.627861. eCollection 2021.

Authors

Xiangning Bai^{1

2}, Ji Zhang³, Ying Hua^{4

5}, Cecilia Jernberg⁶, Yanwen Xiong², Nigel French⁷, Sture Löfgren⁸, Ingela Hedenström⁶, Anoop Ambikan⁴, Sara Mernelius⁸, Andreas Matussek^{4

8

9

10}

Affiliations

¹ Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.
² State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
³ mEpiLab, School of Veterinary Science, Massey University, Palmerston North, New Zealand.
⁴ Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
⁵ Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.
⁶ The Public Health Agency of Sweden, Solna, Sweden.
⁷ New Zealand Food Safety Science and Research Centre, School of Veterinary Science, Massey University, Palmerston North, New Zealand.
⁸ Laboratory Medicine, Jönköping Region County, Department of Clinical and Experimental Medicine, Linköping University, Jönköping, Sweden.
⁹ Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.
¹⁰ Division of Laboratory Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

Shiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens that can cause human infections ranging from asymptomatic carriage to bloody diarrhea (BD) and fatal hemolytic uremic syndrome (HUS). However, the molecular mechanism of STEC pathogenesis is not entirely known. Here, we demonstrated a large scale of molecular epidemiology and in-depth genomic study of clinical STEC isolates utilizing clinical and epidemiological data collected in Region Jönköping County, Sweden, over a 15-year period. Out of 184 STEC isolates recovered from distinct patients, 55 were from patients with BD, and 129 were from individuals with non-bloody stools (NBS). Five individuals developed HUS. Adults were more associated with BD. Serotypes O157:H7, O26:H11, O103:H2, O121:H19, and O104:H4 were more often associated with BD. The presence of Shiga toxin-encoding gene subtypes stx _2a, stx _2a + stx _2c, and stx _1a + stx _2c was associated with BD, while stx ₁ _a was associated with milder disease. Multiplex virulence and accessory genes were correlated with BD; these genes encode toxins, adhesion, autotransporters, invasion, and secretion system. A number of antimicrobial resistance (AMR) genes, such as aminoglycoside, aminocoumarin, macrolide, and fluoroquinolone resistance genes, were prevalent among clinical STEC isolates. Whole-genome phylogeny revealed that O157 and non-O157 STEC isolates evolved from distinct lineages with a few exceptions. Isolates from BD showed more tendency to cluster closely. In conclusion, this study unravels molecular trait of clinical STEC strains and identifies genetic factors associated with severe clinical outcomes, which could contribute to management of STEC infections and disease progression if confirmed by further functional validation.

Keywords: Shiga toxin-producing Escherichia coli; bloody diarrhea; clinical outcomes; comparative genomics; duration of bacterial shedding; whole genome sequencing.