coli triplex B1 strains are prevalent in PID across several locations [32]. However, the evolutionary background of EnPEC is not clear. One possibility is that the endometrial pathogens selleck Tipifarnib may have originated and evolved from intestinal E. coli, as fecal contamination of the vulva and vagina is common. The relationship between EnPEC and DEC or ExPEC requires further exploration before firm conclusions can be drawn. There was little evidence that the uterine E. coli isolates possessed the common pathogenicity genes commonly associated with adhesion, invasion and virulence of DEC or ExPEC although the 17 genes tested only represent a small proportion of the available total [14], [26]. It is noteworthy that the fyuA gene was found in EnPEC but not E. coli from the uterus of clinically unaffected animals.

The fyuA gene encodes the outer membrane protein ferric yersiniabactin uptake that is important for iron uptake and for biofilm formation in UPEC [27], and the scavenging of iron by bacteria in the endometrium may warrant further investigation. The identification of novel pathogenicity genes in EnPEC for the endometrium is likely best accomplished by genome sequencing. Cells recognise LPS via the TLR4/MD-2/CD14 complex and much of the pathology associated with Gram-negative bacteria is associated with the binding of LPS to TLR4 [17]. Endometrial cells challenged with LPS preferentially secrete PGE [18], [19] and the chemokine IL-8, which attracts neutrophils to the endometrium [24]. In the present study, LPS purified from MLST cluster 4 bacteria stimulated the greatest accumulation of PGE or IL-8 in bovine endometrial cells.

Differences in the the cellular inflammatory response between LPS from different E. coli may be associated with structural differences between the LPS of different bacterial strains [33]; or differences in other virulence mechanism that result in exposure of the endometrium to LPS. Endometrial cells isolated from wild type mice also secreted PGE and the chemokine CXCL1, which is the murine chemokine similar to IL-8, in response to LPS from EnPEC but not more than the ultrapure LPS. The cellular response to LPS was abrogated in endometrial cells purified from TLR4?/? mice. These data confirm the important role that TLR4 has in binding LPS during the generation of the innate immune response [17]. Furthermore, it is clear that TLR4 on endometrial epithelial and stromal cells plays an important role in the response to bacterial infection of the uterus and the development of PID [18], [19], [34]. An important observation from the present study was that the EnPEC could cause PID in mice and that the clinical disease was more severe Batimastat when cluster 4 rather than cluster 1 bacteria were infused into the uterine lumen.