title: 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 (GalNAc) catabolism pathway in bacterial pathogenesis. Here, we report the genomic reconstruction of GalN/GalNAc utilization pathway in Streptococci and the diversified aga regulons. We delineated two new paralogous AgaR regulators for the GalN/GalNAc 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 05ZYH33 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/GalNAc 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/GalNAc catabolism pathway to bacterial pathogenesis.
authors.affiliation: Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, L-4360, Luxembourg.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Ravcheev
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cao
authors.affiliation: A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, 127994, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Rodionov
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D000067996:RAW 264.7 Cells; D018085:Regulon; D013290:Streptococcal Infections / Q000382:microbiology*; D017011:Streptococcus suis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D000116:Acetylgalactosamine
keywords: AgaR; N-acetyl-d-galactosamine; Streptococcus suis; amino sugars; d-galactosamine; virulence.