Escherichia coli Type III Secretion System 2 Is Associated With Patient Mortality in Bloodstream Infections

Abstract

Background: Escherichia coli has an extensive accessory genome, though its role in affecting patient mortality is unknown.

Methods: We performed whole genome sequencing with E. coli bacteremia isolates. Pan-genome analysis was used to identify flexible genomic islands associated with in-hospital attributable mortality. Genomic islands of interest were investigated experimentally.

Results: We included 193 E. coli genomes. Two genomic islands were co-present within 41 (21%) genomes and associated with increased attributable mortality in an adjusted analysis (Odds ratio 3.0; 95% confidence interval 1.1-7.9; p=0.03). The two genomic islands together contain genes homologous to a type III secretion system (T3SS): 1) E. coli type III secretion system 2 (ETT2), encoding genes homologous to a T3SS basal body and needle complex, and 2) an ETT2 accessory region (ETT2-AR) encoding genes homologous to a T3SS needle tip, translocases, and adhesin. ETT2/ETT2-AR increased resistance to complement-mediated growth restriction by inhibiting classical complement pathway activation and impacted E. coli-host cell interactions by increasing adhesion to and death of mammalian cells.

Conclusions: Genomic islands ETT2 and ETT2-AR are homologous to a T3SS, co-localize within specific E. coli lineages, associate with increased mortality, and increase bacterial virulence through resistance to complement and enhanced host cell adhesion and death.

Keywords: Escherichia coli; ETT2; bacteremia; bloodstream infection; type III secretion system.