Autophagy and Intracellular Membrane Trafficking Subversion by Pathogenic Yersinia Species

Abstract

Yersinia pseudotuberculosis, Y. enterocolitica and Y. pestis are pathogenic bacteria capable of causing disease in humans by growing extracellularly in lymph nodes and during systemic infections. While the capacity of these bacteria to invade, replicate, and survive within host cells has been known for long, it is only in recent years that their intracellular stages have been explored in more detail. Current evidence suggests that pathogenic Yersinia are capable of activating autophagy in both phagocytic and epithelial cells, subverting autophagosome formation to create a niche supporting bacterial intracellular replication. In this review, we discuss recent results opening novel perspectives to the understanding of intimate host-pathogens interactions taking place during enteric yersiniosis and plague.

Keywords: Y. pestis; Y. pseudotuberculosis; Y. ruckeri; Yersinia enterocolitica; autophagy; enteric yersiniosis; plague.

Figure 1

Summary results from independent studies of autophagy induction by Y. pseudotuberculosis, Y. enterocolitica, and Y. pestis in macrophages. Y. pseudotuberculosis (top) recruits VAMP3 and VAMP7 to the YCV early in the invasion process. VAMP7 facilitates the recruitment of LC3-autophagic membranes, forming an autophagosome with double or multiple membranes. Rab1b (not represented) is important for bacterial survival. Y. pseudotuberculosis survives and replicates in a non-acidic autophagosome. Y. enterocolitica (center) is present in a double- or multiple-membrane autophagosomal compartment positive for LC3. Depending on the strain and its pathogenicity, Y. enterocolitica seems to survive in autophagosomes. Y. pestis (bottom) targets Rab GTPases (1b, 4a, 11b) to the phagosome. Rab1b and Rab4a participate in the inhibition of acidification and thus are involved in bacterial survival. Rab11b is sequestered to the autophagosome over the course of infection, which leads to a global inhibition of host endosomal recycling. Y. pestis proliferates in a non-acidic autophagosome.

Figure 2

Summary results from independent studies of autophagy subversion by enteropathogenic Yersinia in epithelial cells. Y. pseudotuberculosis (left) activates the LAP autophagic pathway during epithelial infection. VAMP3 and VAMP7 are sequentially targeted to the phagosome. VAMP3 favors the commitment towards a single-membrane compartment. VAMP7 participates to the recruitment of LC3-II directly to the phagosome forming the LAPosome. Y. pseudotuberculosis survives and multiplies within a non-acidic single membrane LAPosome. Y. enterocolitica (right) can survive or be degraded in epithelial cells. A subpopulation follows the lysosomal degradative pathway whereas the rest activates the macroautophagy pathway by recruiting LC3-positive autophagic membranes. Galectin-3, a marker of damaged endomembrane, is also recruited to some YCVs, suggesting their potential disruption. Y. enterocolitica survives and replicates in a non-acidic double or multiple membrane autophagosome blocked in its maturation process. The autophagosome seems to support bacterial egress without cell lysis.