Unique Virulence Properties of Yersinia enterocolitica O:3

Essential Role of Invasin for Colonization and Persistence of Yersinia enterocolitica in Its Natural Reservoir Host, the Pig

“…Minipigs were chosen due to their advantages of their handling and housing and their increasing popularity as laboratory animals, as they develop human-sized organs between 6 and 8 months of age (32). First, minipigs were challenged with oral doses of 10 8 , 10 9 , and 10 10 CFU of the O:3 wild-type strain Y1, a recent patient isolate that showed host cell interaction properties identical to other characterized human and porcine isolates (29,30). All pigs appeared healthy and did not show any clinical signs of infection, i.e., increased temperature, diarrhea, or loss of appetite.…”

“…Another difference between O:3 and O:8 is that in O:3 the primary internalization factor, invasin, is highly and (nearly) constitutively synthesized, whereas it is strongly repressed at 37°C in O:8 (30). Constitutive expression of invasin in O:3 was acquired via IS1667 insertion into the rovA regulatory region harboring an IS-specific promoter.…”

“…Constitutive expression of invasin in O:3 was acquired via IS1667 insertion into the rovA regulatory region harboring an IS-specific promoter. Its presence allowed invA expression at 37°C, even in the absence of RovA (30). To test whether constitutive invA expression would be beneficial for O:3, we performed coinfection experiments with the Kan r derivative of the O:3 wild-type strain (YE13) and the Kan s mutant derivative, YE15 (P invO:3⌬IS ), in which the IS1667 element was deleted from the invA promoter region.…”

“…To gain more information about the pathogenic properties of the more frequent Y. enterocolitica O:3 serotypes, we previously compared the colonization mechanisms of different human and animal O:3 isolates with that of the well-characterized Y. enterocolitica O:8 8081v strain and found that Y. enterocolitica O:3 strains have unique cell adhesion and invasion properties (29,30). These differences are mainly attributable to significant variations of the interplay and expression profile of the same repertoire of virulence factors in response to temperature.…”

“…These differences are mainly attributable to significant variations of the interplay and expression profile of the same repertoire of virulence factors in response to temperature. O:3 strains, but not O:8 strains, are able to invade human cells at 37°C due to highly activated and nearly constitutive expression of invasin caused by (i) an additional promoter provided by an IS1667 element inserted in the invA promoter region and (ii) a P98S substitution in the invA transcriptional activator protein RovA that renders the regulator less susceptible to proteolysis by the Lon protease (29,30). In addition, efficient cell attachment by expression of YadA and downregulation of O-antigen synthesis are required to allow InvA-mediated entry into cultured human epithelial cells at body temperature.…”