Genome-wide association studies of Shigella spp. and Enteroinvasive Escherichia coli isolates demonstrate an absence of genetic markers for prediction of disease severity

Abstract

Background: We investigated the association of symptoms and disease severity of shigellosis patients with genetic determinants of infecting Shigella and entero-invasive Escherichia coli (EIEC), because determinants that predict disease outcome per individual patient could be used to prioritize control measures. For this purpose, genome wide association studies (GWAS) were performed using presence or absence of single genes, combinations of genes, and k-mers. All genetic variants were derived from draft genome sequences of isolates from a multicenter cross-sectional study conducted in the Netherlands during 2016 and 2017. Clinical data of patients consisting of binary/dichotomous representation of symptoms and their calculated severity scores were also available from this study. To verify the suitability of the methods used, the genetic differences between the genera Shigella and Escherichia were used as control. Results: The isolates obtained were representative of the population structure encountered in other Western European countries. No association was found between single genes or combinations of genes and separate symptoms or disease severity scores. Our benchmark characteristic, genus, resulted in eight associated genes and > 3,000,000 k-mers, indicating adequate performance of the algorithms used. Conclusions: To conclude, using several microbial GWAS methods, genetic variants in Shigella spp. and EIEC that can predict specific symptoms or a more severe course of disease were not identified, suggesting that disease severity of shigellosis is dependent on other factors than the genetic variation of the infecting bacteria. Specific genes or gene fragments of isolates from patients are unsuitable to predict outcomes and cannot be used for development, prioritization and optimization of guidelines for control measures of shigellosis or infections with EIEC.

Pathogenicity Factors of Genomic Islands in Intestinal and Extraintestinal Escherichia coli

“…Differences in the virulence level have sometimes been put forward, with Shigella considered hyper-virulent relative to EIEC, which generally induces less severe disease. Nevertheless, significant exceptions do exist and the intestinal illness is in fact indistinguishable (Parsot, 2005;Michelacci et al, 2016;Belotserkovsky and Sansonetti, 2018;Hendriks et al, 2020). As with EHEC/STEC, the search for genetic markers that could solely explain the difference in the virulence levels might have somehow hindered the potential in the heterogeneity of the regulation of the genetic expression from one EIEC/Shigella strain to another as well as between individual cells in an isogenic population.…”

Virulence Factors of Enteric Pathogenic Escherichia coli: A Review

“…EIEC/ Shigella infection commences with the penetration of the pathogen into the epithelial cells in the colon, passing through the microfold cells and reaching the underlying submucosa by a transcytosis mechanism [ 78 , 79 ]. The disruption and damage of tight junctions caused by inflammation also give EIEC access to the underlying submucosa [ 80 ].…”

Meat Borne Diseases

“…EIEC strains cause illness that is characterized by watery diarrhea in most patients. Besides, there is a fever, nausea, and abdominal cramps [34].…”