Identification of Virulence Genes Associated with Pathogenicity of Translocating Escherichia coli with Special Reference to the Type 6 Secretion System

Recent genomic characterisation of translocating <i>Escherichia coli</i> HMLN-1 isolated from mesenteric lymph nodes (MLNs) and blood of a patient with a fatal case of pancreatitis revealed the presence of a type 6 secretion system (T6SS) that was not present in non-translocating <i>E. coli</i> strains. This strain was also genomically similar to adherent-invasive <i>E. coli</i> (AIEC) LF82 pathotype. We aimed to identify the role of T6SS-1 in the pathogenesis of this strain and other pathogenic <i>E. coli</i>. The HMLN-1 strain was initially tested for the presence of six virulence genes (VGs) associated with AIEC strains and an iron sequestering system. Additionally, HMLN-1's interaction with a co-culture of Caco-2:HT29-MTX cells and its intra-macrophagic survival was evaluated. We subsequently screened a collection of 319 pathogenic <i>E. coli</i> strains isolated from patients with urinary tract infection (UTI), diarrhoea, inflammatory bowel disease (IBD) and septicaemia for the presence of T6SS-1 and its expression related to adhesion, invasion and translocation via the above co-culture of the intestinal cell lines. The results showed that HMLN-1 harboured four of the AIEC-associated VGs (<i>dsb</i>A, <i>htr</i>A, <i>omp</i>C and <i>afa</i>C). Screening of the pathogenic <i>E. coli</i> collection detected the presence of the T6SS-1 genes in septicaemic and UTI <i>E. coli</i> strains at a significantly higher level than diarrhoea and IBD strains (<i>p</i> < 0.0001). The high expression of T6SS-1 in <i>E. coli</i> HMLN-1 upon adhesion and invasion, as well as its high prevalence among extra-intestinal <i>E. coli</i> strains, suggests a role for T6SS-1 in the pathogenesis of translocating <i>E. coli</i>.