Erythritol alters the expression of genes related to sugar and arginine metabolisms and suppresses the growth of Staphylococcus hyicus

Background: Erythritol, a sugar alcohol, has been reported to suppress the in vitro growth of Staphylococcus pseudintermedius and Staphylococcus coagulans. Objectives: To determine whether erythritol suppresses the growth of Staphylococcus hyicus, a major pathogen causing porcine exudative epidermitis, and to investigate the molecular mechanisms involved in erythritol-induced S. hyicus growth suppression. Materials and Methods: An in vitro turbidity assay was performed to assess the effect of erythritol on the growth of 26 S. hyicus strains, including a reference strain JCM 2423 and the 25 wild strains isolated from pigs. Differentially expressed genes in response to erythritol in JCM 2423 were identified by RNA-Seq and quantitative reverse transcription-PCR. The impact of trehalose, glucose and arginine supplementation on erythritol-induced growth suppression of the 25 S. hyicus wild strains was also investigated. Results: Erythritol suppressed the in vitro growth of JCM 2423 and the 25 S. hyicus wild strains. Moreover, erythritol upregulated the transcription of multiple genes in JCM 2423, including those encoding ATP-binding cassette transporter enzymes (potB, potC and potD), arginine biosynthetic pathway enzymes (argF, argG and argH), l-arginine deiminase pathway enzymes (arcA, arcC and arcD), fatty acid metabolism pathway enzymes (fabH and fabF) and trehalose metabolism-related proteins (treC, treR and treP). Supplementation of trehalose or glucose in aerobic conditions or arginine supplementation in anaerobic conditions restored in vitro growth of the 25 S. hyicus wild strains treated by erythritol. Conclusions and Clinical Relevance: Erythritol suppresses the in vitro growth of S. hyicus by inhibiting intracellular sugar and arginine metabolism under aerobic and anaerobic conditions, respectively.