Fig 1: Identifying more MSE-ExT effectors across the S. suis. (a) Phylogenetic analysis of 104 randomly selected MSE-ExT effectors wildly encoded in S. suis isolates. A neighbor-joining tree was constructed based on the C-terminal extension of MSE-ExT effectors using the MEGA software version 7.0. Detailed information is shown in Supplementary Figure S4 . (b, c) Identification of the antibacterial activities of MSE-ExT7 and -ExT12 using the outcome of interbacterial competition assays between the indicated S. suis donor and recipient strains. Details are provided in the legend to Figure 1d . (d) Identification of MSE-ExT effectors harboring diverse NADase toxins in S. suis isolates. Ribbon depiction showing the superimposition of AlphaFold3-predicted ExT (colored purple) and the corresponding best-matching template (colored gray) is presented on the right, and detailed information is shown in Supplementary Figure S8 . All of the best-matching templates were annotated as NADases at the bottom of the phylogenetic tree, their NAD+-consuming activities are classified into four varieties (triangles marked in four different colors) as in previous studies (Roussin and Salcedo, 2021), and their cleavage sites and products were exhibited by diagrams on the right. #The annotated function is only predicted but lacks experimental validation. (e) Relative NAD+ levels were measured using the NAD/NADH Assay Kit (Colorimetric, ab65348, Abcam) in E. coli cytoplasm expressing the indicated proteins. Tse2 and Tse6 were used as the negative and positive controls as in a previous report (Jc et al., 2017), respectively. (b, c, e) Error bars represent the mean ± SD of three biological repeats. ***P < 0.001.