Pathogen-mediated posttranslational modifications: A re-emerging field

Abstract

Posttranslational modifications are increasingly recognized as key strategies used by bacterial and viral pathogens to modulate host factors critical for infection. A number of recent studies illustrate how pathogens use these posttranslational modifications to target central signaling pathways in the host cell, such as the NF-kB and MAP kinase pathways, which are essential for pathogens' replication, propagation, and evasion from host immune responses. These discoveries open new avenues for investigating the fundamental mechanisms of pathogen infection and the development of new therapeutics.

Figure 1

Posttranslational Modification of Host Proteins during Infection Yersinia (blue) is an extracellular pathogen that injects effectors into the host cell's cytoplasm using a specialized type III secretion system (T3SS). Salmonella (red) triggers its own entry into host cells and replicates in a remodeled vacuole. It also secretes T3SS-dependent effectors. After cell invasion, Listeria (green) escapes from vacuoles and resides free in the cytoplasm, where it replicates and starts moving using the host cell's actin. Interactions with host factors are mediated by bacterial surface or secreted proteins. Effectors from all three of these bacteria (blue for Yersinia effectors, red for Salmonella effectors, and green for Listeria effectors) alter posttranslational modifications of host proteins (purple) to facilitate pathogens' replication, propagation, and evasion from host immune responses .

Figure 2

Pathogen-Mediated PTMs Target the Cytoskeleton and Immunoreceptors Bacteria effector proteins (green) control the dynamics of the host cell's actin cytoskeleton by posttranslationally modifying Rho-GTPases (left). Viral effector proteins (blue) regulate posttranslational modification of immunoreceptors, such as the major histocompatibility complex class I (MHC I) and the CD4 (cluster of differentiation 4) molecules (right), thereby decreasing their expression at the cell surface and dampening immune responses.

Figure 3

Pathogen-Mediated PTMs Target the MAP Kinase and NF-κB Signaling Pathways The MAP kinase (left) and NF-κB (right) signaling cascades trigger immune responses in the host cell during infections. Both bacterial (green) and viral (blue) effectors weaken these immune responses by inducing or counteracting posttranslational modifications of key components in these critical pathways.