Yersinia infection tools—characterization of structure and function of adhesins

Abstract

Among the seventeen species of the Gram-negative genus Yersinia, three have been shown to be virulent and pathogenic to humans and animals—Y. enterocolitica, Y. pseudotuberculosis, and Y. pestis. In order to be so, they are armoured with various factors that help them adhere to tissues and organelles, cross the cellular barrier and escape the immune system during host invasion. The group of proteins that mediate pathogen–host interactions constitute adhesins. Invasin, Ail, YadA, YadB, YadC, Pla, and pH 6 antigen belong to the most prominent and best-known Yersinia adhesins. They act at different times and stages of infection complementing each other by their ability to bind a variety of host molecules such as collagen, fibronectin, laminin, β1 integrins, and complement regulators. All the proteins are anchored in the bacterial outer membrane (OM), often forming rod-like or fimbrial-like structures that protrude to the extracellular milieu. Structural studies have shown that the anchor region forms a β-barrel composed of 8, 10, or 12 antiparallel β-strands. Depending on the protein, the extracellular part can be composed of several domains belonging to the immunoglobulin fold superfamily, or form a coiled-coil structure with globular head domain at the end, or just constitute several loops connecting individual β-strands in the β-barrel. Those extracellular regions define the activity of each adhesin. This review focuses on the structure and function of these important molecules, and their role in pathogenesis.

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…The yadA gene is an adhesion that interacts with the extracellular matrix to promote attachment of Y. pseudotuberculosis and Y. enterocolitica to the host cell [24][25][26]. Invasin is a highly efficient molecule that binds β1-intergrins to facilitate uptake of both Y. pseudotuberculosis and Y. enterocolitica by the host through "outside-in" signaling [26][27][28][29]. Even though Y. pestis lost these conserved factors the bacterium acquired additional virulence factors that contribute heavily to the organism's life cycle.…”

“…The zipper mechanism occurs when bacterial proteins bind host membrane proteins creating an internalization signal ("outside-in") that induces the bacteria's uptake [260,261]. An example of this is Invasin, a conserved molecule between Y. pseudotuberculosis and Y. enterocolitica that binds β1 intergrins [26,28,29,262,263]. Through clustering of β1 intergrins on the host cell surface the enteric…”

“…pestis has several known adhesins, such as Ali, YadB, YadC, Pla and pH 6 antigen [1,26,265]. Studies of these adhesins in Y. pestis demonstrate their importance for adhering to host epithelial cells and professional phagocytes through interactions with host proteins, but clear links indicating their role in Y. pestis invasion has not been established [26,[265][266][267]. Furthermore, the Y. pestis T3SS is not used for invasion, and is actually well established to be anti-phagocytic [1].…”

Characterizing the virulence factor YapE in Yersinia pestis.

“…It has been linked to invasion of host immune cells and dissemination by its interaction with CD205 on macrophages [72]. A pla mutant is attenuated in a mammalian host due to both its inability to disseminate from the site of infection and through its uptake by macrophages.…”

“…YadB and YadC have the ability to form oligomers that lead to aggregation and mediate invasion to epithelial cells, although they are not necessary for host cell adherence [72,73]. Studies have shown that when both proteins are mutated, there is a substantial decrease in the ability for the bacteria to invade HeLa cells and type I pneumocytes, but does not affect overall adherence to cells [73].…”