Furthermore, the EnPEC also colonised the endometrium and invaded throughout the uterine wall. A mouse model of PID may be useful to study host-pathogen interactions and the mechanisms of infection and immunity in the endometrium. The present work has most relevance for PID in cattle rather than humans research only because the bacteria infecting the upper female genital tract differ between species [1], [3], [6], [7]. However, an in vivo model for the endometrium per se is important because mucosal immunity mechanisms in the endometrium appear to be different from the other commonly studied mucosa such as the intestinal or respiratory tracts, and are closely regulated by ovarian steroids [35], [36]. In conclusion, the present study counters the previous hypothesis that bacteria causing PID are genetically diverse isolates from the feces or environment that randomly infect the reproductive tract.

Here we have identified for the first time specific strains and clonal groups of E. coli that posses a pathogenic potential for causing PID in cattle, which we call endometrial pathogenic E. coli (EnPEC). The clusters of E. coli identified using MLST differed from reference strains of E. coli, including DEC, ExPEC and a bovine mastitis strain, but further genotyping is required to understand their origins. The EnPEC did not posses invasins, adhesins and virulence genes typical of DEC- or ExPEC, except for fyuA, which is associated with iron scavenging. The E. coli strains associated with PID were most adherent and invasive for endometrial cells. These E.

coli stimulated a host cell immune response, which was at least in part mediated by LPS binding to TLR4 on endometrial cells. The EnPEC were also used to establish a murine model of PID but whether EnPEC cause disease in humans requires investigation. The implications of the findings from the present study provide a paradigm shift for development of vaccines or biological therapeutics for PID, which should specifically target EnPEC rather than other strains of E. coli. Materials and Methods Ethics Statement All procedures were conducted under the UK Animal Scientific Procedures Act (1986) with the approval of the UK Government Home Office, the Royal Veterinary College Local Ethical Review Committee and Swansea University Ethical Review Process committee. Collection of E.

coli from the Uterus All procedures were conducted under the UK Animal Scientific Procedures Act (1986) with the approval of the UK Government Home Drug_discovery Office and the Royal Veterinary College Local Ethical Review Committee. All postpartum Holstein-Friesian cows in the Royal Veterinary College dairy herd (median parity 3; range: 1 to 7) were maintained under standard conditions and examined as described during a one-year period [6]. Animals with non-uterine bacterial infections were excluded.