[en] 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.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Molecular Systems Physiology (Thiele Group)
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Zhang, Huimin
Ravcheev, Dmitry ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Hu, Dan
Zhang, Fengyu
Gong, Xiufang
Hao, Lina
Cao, Min
Rodionov, Dmitry A.
Wang, Changjun
Feng, Youjun
External co-authors :
yes
Language :
English
Title :
Two novel regulators of N-acetyl-galactosamine utilization pathway and distinct roles in bacterial infections