Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors

Abstract

Several bacterial species have evolved specialized secretion systems to deliver bacterial effector proteins into eukaryotic cells. These effectors have the capacity to modulate host cell pathways in order to promote bacterial survival and replication. The spatial and temporal context in which the effectors exert their biochemical activities is crucial for their function. To fully understand effector function in the context of infection, we need to understand the mechanisms that lead to the precise subcellular localization of effectors following their delivery into host cells. Recent studies have shown that bacterial effectors exploit host cell machinery to accurately target their biochemical activities within the host cell.

Fig. 1

A number of intracellular bacteria have evolved specialized secretion systems to deliver bacterial effector proteins into eukaryotic cells. These effector proteins modulate host cell pathways to promote bacterial survival and replication. Once translocated into the host cell cytosol, many bacterial effector proteins (some of them depicted in this diagram) exploit eukaryotic-host cell machinery to reach their final subcellular localization. L. pneumophila utilizes a T4SS to deliver phosphoinositide-binding effectors, including SidC, SidM, and SetA, which recruit host cell membrane to the Legionella-containing vacuole (LCV) to help establish an intracellular replication niche. The Enteropathogenic Escherichia coli (EPEC) T3SS effectors, Map and EspF encode putative N-terminal mitochondrial targeting signals, and when transiently expressed in eukaryotic cells, localize to mitochondria by interacting with components of the classical mitochondrial import machinery. The plant pathogen, Xanthomonas translocates a family of effectors, including AvrBs3, which localize to the plant nucleus where they alter host gene expression during infection. These effectors encode a classic nuclear localization signal (NLS) that is recognized by the host cell nuclear import pathway leading to their nuclear targeting. The Salmonella T3SS effector, SopB, requires host-mediated monoubiquitination to localizes to the salmonella-containing vacuole (SCV) late during infection. Salmonella also utilizes host-mediated lipidation to target effectors to their site of action. Salmonella effector, SspH2 is S-palmitoylated by host enzymes resulting in its plasma membrane localization. Another Salmonella effector, SifA, is both S-palmitoylated and prenylated resulting in localization to the SCV.