Supplemental_Datasets

Salmonella employs multiple pathways to secrete proteins, facilitating bacterial interactions with hosts, invasions and pathogenicity. Not like type III secretion systems (T3SSs) and the effectors, type I secretion systems (T1SSs) and the substrates have not been investigated extensively in Salmonella, despite their potential significance. In this research, we adopted a homology-searching based strategy to screen 61 sets of T1SSs from the genomes of 26 representative strains covering the known Salmonella species and subspecies. The T1SSs fall into 4 clusters. Cluster I and Cluster II T1SSs are conserved and were potentially acquired anciently before the diversification of the Salmonella genus, Cluster III T1SSs were also anciently obtained but lost in many S. enterica subspecies and strains, and Cluster IV T1SSs are unconserved and could have been acquired by individual strains through horizontal transferring events. Cluster I and II T1SS gene clusters form independent operons lacking local transcription regulator genes nearby the genomic loci, but both were well adapted to the bacterial global transcriptional regulation networks. The Cluster I T1SS operon is involved in a large network participating in basic biological processes of the bacterial cell, while the Cluster II T1SS operon is transcriptionally co-regulated with the operons of Salmonella Pathogenic Island 1 (SPI-1) T3SS gene cluster, the effector genes, and other virulence genes. HilC was found to be a potential key regulator for the co-expression network of the Cluster II T1SS operon. Finally, with the features of gene evolution, operon co-expression and secretion signal sequences, we predicted 159 potential T1SS substrate proteins from the strains. It was noticed that the putative Cluster II T1SS substrates, SiiE family proteins, showed apparent sequence diversity. Taken together, the study comprehensively investigated the distribution, evolution, regulation and the secreted proteins of T1SSs in Salmonella, broadening our knowledge about the bacterial biology, survival and interactions with hosts.