Supplemental_Datasets

<i>Salmonella</i> 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 <i>Salmonella</i>, 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 <i>Salmonella</i> 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 <i>Salmonella</i> genus, Cluster III T1SSs were also anciently obtained but lost in many <i>S. enterica</i> 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 <i>Salmonella</i> 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 <i>Salmonella</i>, broadening our knowledge about the bacterial biology, survival and interactions with hosts.

沙门氏菌属（Salmonella）可通过多条分泌通路介导蛋白分泌，进而实现与宿主的相互作用、细菌入侵及致病过程。与III型分泌系统（T3SSs）及其效应蛋白不同，尽管I型分泌系统（T1SSs）及其底物具有潜在重要研究价值，但目前沙门氏菌属中针对此类系统及底物的研究仍不够深入。本研究采用基于同源搜索的筛选策略，从覆盖已知沙门氏菌属所有物种和亚种的26株代表性菌株的基因组中，共筛选得到61套I型分泌系统。该类分泌系统可划分为4个簇：簇I与簇II的I型分泌系统序列保守，推测在沙门氏菌属物种分化前便已远古获得；簇III的I型分泌系统同样起源远古，但在多数肠炎沙门氏菌亚种及菌株中发生了丢失；簇IV的I型分泌系统不具备保守性，推测是通过水平基因转移事件由单个菌株获得的。簇I与簇II的I型分泌系统基因操纵子均为独立转录单元，其基因组位点附近未编码本地转录调控基因，但二者均适配于细菌的全局转录调控网络。其中，簇I的I型分泌系统操纵子参与构成细菌细胞基础生物学过程的大型调控网络；而簇II的I型分泌系统操纵子则与沙门氏菌致病岛1（SPI-1）的III型分泌系统基因簇操纵子、效应基因及其他毒力基因共同受到转录共调控。研究发现，HilC是调控簇II I型分泌系统操纵子共表达网络的潜在关键调控因子。最后，本研究结合基因进化特征、操纵子共表达特征以及分泌信号序列，从供试菌株中预测得到159个潜在的I型分泌系统底物蛋白。其中，推测隶属于簇II I型分泌系统底物的SiiE家族蛋白展现出显著的序列多样性。综上，本研究全面解析了沙门氏菌属中I型分泌系统的分布、进化、调控机制及其分泌蛋白组，拓宽了我们对该细菌生物学特性、生存策略以及宿主相互作用的认知。