PLoS Pathog. http://dx.doi.org/10.1371/journal.ppat.1005552 (2016)

Salmonella typhimurium utilizes a type III secretion system to deliver bacterial effector proteins such as the E3 ligase SopA into host cells. These effectors induce inflammation in the host and co-opt host function in the intestinal epithelium. In order to understand how SopA effects changes in host signal transduction pathways that lead to inflammation, Kamanova et al. first used affinity purification to identify two host E3 ubiquitin ligases, TRIM56 and TRIM65, as SopA-binding proteins during infection. SopA enzymatic activity enhanced TRIM65 ubiquitylation but did not target TRIM65 for proteasome-mediated degradation. Instead, the authors found that TRIM65 ubiquitin ligase activity was required to promote interactions with the innate immune receptor MDA5 to modulate expression of the proinflammatory cytokine interferon-β. SopA also increased the ability of TRIM56 to stimulate interferon-β expression through RIG-1, another innate immune receptor, and increased the expression of other proinflammatory cytokines in mice infected with S. typhimurium. These results suggest a mechanism whereby bacterial SopA acts through host ubiquitin ligases to mediate host inflammation via two major innate immune receptor pathways, and benefiting the bacteria by providing essential nutrients for growth.