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.