AUTHOR=Deng Zhongliang , Liu Zizhong , He Junming , Wang Jing , Yan Yanfeng , Wang Xiaoyi , Cui Yujun , Bi Yujing , Du Zongmin , Song Yajun , Yang Ruifu , Han Yanping 

TITLE=TyrR, the regulator of aromatic amino acid metabolism, is required for mice infection of Yersinia pestis

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00110

DOI=10.3389/fmicb.2015.00110

ISSN=1664-302X

ABSTRACT=<p><italic>Yersinia pestis</italic>, the causative agent of plague, poses a serious health threat to rodents and human beings. TyrR is a transcriptional regulator (TyrR) that controls the metabolism of aromatic amino acids in <italic>Escherichia coli</italic>. In this paper, TyrR played an important role in <italic>Y. pestis</italic> virulence. Inactivation of <italic>tyrR</italic> did not seem to affect the <italic>in vitro</italic> growth of this organism, but resulted in at least 10,000-fold attenuation compared with the wild-type (WT) strain upon subcutaneous infection to mice. In addition, loads of <italic>tyrR</italic> mutant within mice livers and spleens significantly decreased compared with the WT strain. Transcriptome analysis revealed that TyrR, directly or indirectly, regulated 29 genes encoded on <italic>Y. pestis</italic> chromosome or plasmids under <italic>in vitro</italic> growth condition. Similar to the regulatory function of this protein in <italic>E. coli</italic>, five aromatic-pathway genes (<italic>aroF-tyrA</italic>, aroP, <italic>aroL</italic>, and <italic>tyrP</italic>) were significantly reduced upon deletion of the <italic>tyrR</italic> gene. Two genes (<italic>glnL</italic> and <italic>glnG</italic>) that encode sensory histidine kinase and regulator in a two-component regulatory system involved in nitrogen assimilation were downregulated in the <italic>tyrR</italic> mutant. Several genes encoding type III secretion proteins were transcribed by 2.0–4.2-fold in a <italic>tyrR</italic> mutant relative to the WT strain. Interestingly, the acid-stressed genes, <italic>hdeB</italic> and <italic>hdeD</italic>, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the <italic>tyrR</italic> mutant under acidic conditions. In conclusion, regulation of TyrR in <italic>Y. pestis</italic> is similar to, but distinct from, that in <italic>E. coli</italic>. TyrR is a metabolic virulence determinant in <italic>Y. pestis</italic> that is important for extracellular survival and/or proliferation.</p>