Proteomic and Metabolomic Analyses Provide Insights into the Mechanism on Arginine Metabolism Regulated by tRNA Modification Enzymes GidA and MnmE of Streptococcus suis

Abstract

GidA and MnmE, two important tRNA modification enzymes, are contributed to the addition of the carboxymethylaminomethyl (cmnm) group onto wobble uridine of tRNA. GidA-MnmE modification pathway is evolutionarily conserved among Bacteria and Eukarya, which is crucial in efficient and accurate protein translation. However, its function remains poorly elucidated in zoonotic Streptococcus suis (SS). Here, a gidA and mnmE double knock-out (DKO) strain was constructed to systematically decode regulatory characteristics of GidA-MnmE pathway via proteomic. TMT labelled proteomics analysis identified that many proteins associated with cell divison and growth, fatty acid biosynthesis, virulence, especially arginine deiminase system (ADS) responsible for arginine metabolism were down-regulated in DKO mutant compared with the wild-type (WT) SC19. Accordingly, phenotypic experiments showed that the DKO strain displayed decreased in arginine consumption and ammonia production, deficient growth, and attenuated pathogenicity. Moreover, targeted metabolomic analysis identified that arginine was accumulated in DKO mutant as well. Therefore, these data provide molecular mechanisms for GidA-MnmE modification pathway in regulation of arginine metabolism, cell growth and pathogenicity of SS. Through proteomic and metabolomic analysis, we have identified arginine metabolism that is the links between a framework of protein level and the metabolic level of GidA-MnmE modification pathway perturbation.

LC_Glucose-Inhibited Division Protein Is Required for Motility, Biofilm Formation, and Stress Response in Lysobacter capsici X2-3

“…tRNA modification ensures efficient and accurate protein synthesis and promotes cellular health and growth ( Manickam et al, 2016 ). Glucose-inhibited division protein (GidA), which is highly conserved in prokaryotes, serves as a tRNA modification enzyme and catalyzes the addition of a carboxymethylaminomethyl (cmnm) group at the 5′ position of the wobble uridine (U34) of tRNAs ( Yu et al, 2019 ; Gao et al, 2020 ). GidA modification is evolutionarily conserved in bacteria and Eukarya, which is essential for efficient and accurate protein translation ( Fislage et al, 2014 ).…”

Exogenous glycogen utilization effects the transcriptome and pathogenicity of Streptococcus suis serotype 2

“…Our data showed that the central metabolism shifts from the glycolysis pathway toward the PPP in S. suis after glycogen induction ( Figure 3 ) and presents the possible stress responses of S. suis under glycogen-induced conditions. Moreover, the increased ADS ( Table 3 ) can catalyze the conversion of arginine to ornithine, thereby producing ammonia, carbon dioxide, and ATP, which provides energy and protection for S. suis during stress ( Gao et al., 2020 ).…”

Peptidomics Analysis of Virulent Peptides Involved in Streptococcus suis Pathogenesis

“…In the present study, a derived peptide of 3-oxoacyl-[acyl-carrier-protein] reductase responsible for the fatty acid biosynthesis was identified in SS2, SS14, SS7, and SS27. The previous studies demonstrated that this enzyme was associated with the fatty acid biosynthesis of virulent SS2 [ 27 , 28 ]. Thus, we could assume that this fatty acid biosynthesis-associated enzyme is significant for S. suis adaptation in the host-simulated environment.…”