Genomic and phenotypic analysis of SspH1 identifies a new Salmonella effector, SspH3

Salmonella is a major foodborne pathogen and is responsible for a range of diseases. Not all Salmonella contributes to severe health outcomes as there is a large degree of genetic heterogeneity among the 2,600 serovars within the genus. This variability across Salmonella serovars is linked to numerous genetic elements that dictate virulence. While several genetic elements encode virulence factors with well-documented contributions to pathogenesis, many genetic elements implicated in Salmonella virulence remain uncharacterized. Many pathogens encode a family of E3 ubiquitin ligases that are delivered into the cells that they infect using a Type 3 Secretion System (T3SS). These effectors, known as NEL-domain E3s, were first characterized in Salmonella. Most Salmonella encodes the NEL-effectors sspH2 and slrP, whereas only a subset of Salmonella encodes sspH1. SspH1 has been shown to ubiquitinate the mammalian protein kinase PKN1, which has been reported to negatively regulate the pro-survival program Akt. We discovered that SspH1 mediates the degradation of PKN1 during infection of a macrophage cell line but that this degradation does not impact Akt signaling. Genomic analysis of a large collection of Salmonella genomes identified a putative new gene, sspH3, with homology to sspH1. SspH3 is a novel NEL-domain effector.