Two novel regulators of N‐acetyl‐galactosamine utilization pathway and distinct roles in bacterial infections

Abstract

Bacterial pathogens can exploit metabolic pathways to facilitate their successful infection cycles, but little is known about roles of d‐galactosamine (GalN)/ N‐acetyl‐ d‐galactosamine (Gal NAc) catabolism pathway in bacterial pathogenesis. Here, we report the genomic reconstruction of GalN/Gal NAc utilization pathway in Streptococci and the diversified aga regulons. We delineated two new paralogous AgaR regulators for the GalN/Gal NAc catabolism pathway. The electrophoretic mobility shift assays experiment demonstrated that AgaR2 (AgaR1) binds the predicted palindromes, and the combined in vivo data from reverse transcription quantitative polymerase chain reaction and RNA‐seq suggested that AgaR2 (not AgaR1) can effectively repress the transcription of the target genes. Removal of agaR2 (not agaR1) from Streptococcus suis 05 ZYH33 augments significantly the abilities of both adherence to Hep‐2 cells and anti‐phagocytosis against RAW264.7 macrophage. As anticipated, the dysfunction in AgaR2‐mediated regulation of S. suis impairs its pathogenicity in experimental models of both mice and piglets. Our finding discovered two novel regulators specific for GalN/Gal NAc catabolism and assigned them distinct roles into bacterial infections. To the best of our knowledge, it might represent a first paradigm that links the GalN/Gal NAc catabolism pathway to bacterial pathogenesis.