Subversion of MAPK signaling by pathogenic bacteria

Abstract

Bacterial components are recognized by host pattern recognition receptors that trigger signaling cascades, leading to inflammation and eradication of the bacteria. The main proinflammatory signaling pathway is the MAP kinase (MAPK)/NF-kB interwoven cascades, which result in transcription of pro-inflammatory genes. Many bacteria have evolved to interfere with the immune response through a mechanism that involves delivery of virulent proteins to the host cells. These proteins posttranslationally modify key components in the host signaling cascades. This review will describe bacterial strategies to directly manipulate host MAPK signaling, summarizing recent discoveries in the field.

The Puccinia striiformis effector Hasp98 facilitates pathogenicity by blocking the kinase activity of wheat TaMAPK4

“…The effectors HopAI1 and OspF specifically modify phosphothreonine in the TXY motif of the MAPK activation ring. Whereas traditional phosphatases hydrolyze the Co‐P bond and produce a hydroxyl group, which can be re‐phosphorylated, OspF, and HopAI1 specifically cleave the C‐OP bond in the phosphothreonine in the TXY motif, thereby irreversibly inactivating MAPKs (Gur Arie and Rosenshine, 2015). Here, we confirmed that the TEY motif is important for the kinase activity of TaMAPK4.…”

The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases

“…The opportunistic bacterial pathogen Pseudomonas aeruginosa-encoded ExoS, a virulence factor produced and secreted directly into the host cell by the type III secretion system (T3SS), also activates JNK phosphorylation and triggers cellular apoptosis depending on the subsequent JNK-mediated signaling [80] (Figure 4). In addition, many bacteria have evolved strategies to manipulate and subvert host MAPK signaling through translocated effector proteins that directly catalyze the posttranslational modification of proteins in the MAPK network [81] (Figure 4). The AvrA protein in Salmonella typhimurium is an important Salmonella effector protein secreted by the Salmonella T3SS that directs acetyltransferase activity toward specific host MAPKKs, inhibiting signaling through the host JNK/AP-1 pathway and dampening the pro-apoptotic innate immune response [82].…”

Constant vigilance: plant functions guarded by resistance proteins

“…Unrelated effectors from different human pathogens with distinct activities, including phosphatases, methyl‐transferases, acetyltransferases, and proteases were found to disturb MAPK cascades (Gur‐Arie and Rosenshine, ). Targeting MAPK signaling cascades by pathogen effectors seems to be a common strategy to suppress innate immunity.…”

“…The uridylylation of PBL2, a homolog of BIK1 and host decoy, can be recognized by a protein complex formed by the pseudokinase RKS1 and the R protein ZAR1, resulting in an ETI response. transferases, acetyltransferases, and proteases were found to disturb MAPK cascades (Gur-Arie and Rosenshine, 2015). Targeting MAPK signaling cascades by pathogen effectors seems to be a common strategy to suppress innate immunity.…”

“…Moreover, BIK1 activation also causes downstream activation of two distinct MAPK cascades, the MEKK1–MKK1/MKK2–MPK4 cascade and the MKK4/MKK5–MPK3/MPK6 cascade, each with different downstream products and responses. MAPK cascades are conserved among eukaryotes, playing a central role in both plant and animal innate immunity (Meng and Zhang, ; Gur‐Arie and Rosenshine, ).…”