A systematic survey of type I secretion systems and their substrate proteins in Salmonella.

Type I secretion systems (T1SSs) and the substrates have not been investigated extensively in Salmonella, despite their potential significance. In this research, we screened the comprehensive list of Salmonella T1SSs, observed their evolution and transcriptional regulation, predicted the substrates and explored their sequence and structural properties. In total, 61 sets of T1SSs were captured from the genomes of 26 representative strains covering the known Salmonella species and subspecies. The T1SSs fall into 4 clusters. Clusters I and II are conserved and were potentially acquired anciently before the diversification of the Salmonella genus, Cluster III was also anciently acquired but lost in many S. enterica subspecies and strains, and Cluster IV is unconserved and could have been acquired by individual strains through horizontal transferring events. The Cluster II T1SS gene cluster is transcriptionally co-regulated with the operons of Salmonella Pathogenic Island 1 (SPI-1) type III secretion system (T3SS) gene cluster, the effector genes, and other virulence genes, while HilC could potentially be a key regulator for the network. We also predicted 159 potential T1SS substrates from the strains. The putative SiiE-family Cluster II T1SS substrates showed apparent sequence diversity, attributed to recombination, gene fission, fragmental deletion, and point mutation. However, the variants of SiiE proteins appeared structurally conserved and secretable through T1SS conduits, including the two shorter peptides derived from the split siiE genes in S. Typhi strains. Taken together, the study broadened our knowledge about the T1SSs in Salmonella, their evolution and the SiiE-mediated bacterial pathogenicity.