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

Deng Z, Liu Z, He J, Wang J, Yan Y, Wang X, Cui Y, Bi Y, Du Z, Song Y, Yang R, Han Y - Front Microbiol (2015)

Bottom Line: Similar to the regulatory function of this protein in E. coli, five aromatic-pathway genes (aroF-tyrA, aroP, aroL, and tyrP) were significantly reduced upon deletion of the tyrR gene.Interestingly, the acid-stressed genes, hdeB and hdeD, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the tyrR mutant under acidic conditions.In conclusion, regulation of TyrR in Y. pestis is similar to, but distinct from, that in E. coli.

View Article: PubMed Central - PubMed

Affiliation: Department of Sanitary Inspection, School of Public Health, University of South China Hengyang, China ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.

ABSTRACT
Yersinia pestis, 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 Escherichia coli. In this paper, TyrR played an important role in Y. pestis virulence. Inactivation of tyrR did not seem to affect the in vitro 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 tyrR 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 Y. pestis chromosome or plasmids under in vitro growth condition. Similar to the regulatory function of this protein in E. coli, five aromatic-pathway genes (aroF-tyrA, aroP, aroL, and tyrP) were significantly reduced upon deletion of the tyrR gene. Two genes (glnL and glnG) that encode sensory histidine kinase and regulator in a two-component regulatory system involved in nitrogen assimilation were downregulated in the tyrR mutant. Several genes encoding type III secretion proteins were transcribed by 2.0-4.2-fold in a tyrR mutant relative to the WT strain. Interestingly, the acid-stressed genes, hdeB and hdeD, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the tyrR mutant under acidic conditions. In conclusion, regulation of TyrR in Y. pestis is similar to, but distinct from, that in E. coli. TyrR is a metabolic virulence determinant in Y. pestis that is important for extracellular survival and/or proliferation.

No MeSH data available.


Related in: MedlinePlus

Effect of the tyrR gene on Y. pestis pathogenesis in mice. Groups of five or seven BALB/c mice were inoculated by subcutaneous injection with appropriated dose of Y. pestis strain 201 (open circles), 47-kb mutant (filled diamonds), tyrR (filled triangles) or tyrR complementary strain (filled circles). Mice mortality was monitored for 14 d.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4325908&req=5

Figure 1: Effect of the tyrR gene on Y. pestis pathogenesis in mice. Groups of five or seven BALB/c mice were inoculated by subcutaneous injection with appropriated dose of Y. pestis strain 201 (open circles), 47-kb mutant (filled diamonds), tyrR (filled triangles) or tyrR complementary strain (filled circles). Mice mortality was monitored for 14 d.

Mentions: We observed the strong attenuation of a deletion mutant of ~47-kb DNA fragment containing more than 40 genes in BALB/c mice upon subcutaneous inoculation. To trace which gene(s) or operon is responsible for the attenuated phenotype, DNA fragments within the 47-kb region were knockout one by one from the WT strain. The resulting mutants were subject to mice infection, respectively. Finally, a ~8-kb fragment containing tyrR and its flanking sequences were confirmed to be the main reason for the virulence phenotype. Therefore, we decided to assess the roles of TyrR protein in Y. pestis pathogenesis. Mice were infected subcutaneously (s.c.) with increasing numbers of WT, tyrR mutant, and complementary strain to estimate the virulence by calculating LD50. The LD50 of both the WT strain 201 and the tyrR complementary strain was, <8 CFU, but up to about 8 × 104 cells of the tyrR mutant was not lethal to s.c. inoculated mice (Figure 1). The observation suggested that the significantly attenuated virulence of the tyrR mutant is due to the lack of TyrR protein rather than to polar effects caused by the insertion of a kanamycin resistance cassette.


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

Deng Z, Liu Z, He J, Wang J, Yan Y, Wang X, Cui Y, Bi Y, Du Z, Song Y, Yang R, Han Y - Front Microbiol (2015)

Effect of the tyrR gene on Y. pestis pathogenesis in mice. Groups of five or seven BALB/c mice were inoculated by subcutaneous injection with appropriated dose of Y. pestis strain 201 (open circles), 47-kb mutant (filled diamonds), tyrR (filled triangles) or tyrR complementary strain (filled circles). Mice mortality was monitored for 14 d.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325908&req=5

Figure 1: Effect of the tyrR gene on Y. pestis pathogenesis in mice. Groups of five or seven BALB/c mice were inoculated by subcutaneous injection with appropriated dose of Y. pestis strain 201 (open circles), 47-kb mutant (filled diamonds), tyrR (filled triangles) or tyrR complementary strain (filled circles). Mice mortality was monitored for 14 d.
Mentions: We observed the strong attenuation of a deletion mutant of ~47-kb DNA fragment containing more than 40 genes in BALB/c mice upon subcutaneous inoculation. To trace which gene(s) or operon is responsible for the attenuated phenotype, DNA fragments within the 47-kb region were knockout one by one from the WT strain. The resulting mutants were subject to mice infection, respectively. Finally, a ~8-kb fragment containing tyrR and its flanking sequences were confirmed to be the main reason for the virulence phenotype. Therefore, we decided to assess the roles of TyrR protein in Y. pestis pathogenesis. Mice were infected subcutaneously (s.c.) with increasing numbers of WT, tyrR mutant, and complementary strain to estimate the virulence by calculating LD50. The LD50 of both the WT strain 201 and the tyrR complementary strain was, <8 CFU, but up to about 8 × 104 cells of the tyrR mutant was not lethal to s.c. inoculated mice (Figure 1). The observation suggested that the significantly attenuated virulence of the tyrR mutant is due to the lack of TyrR protein rather than to polar effects caused by the insertion of a kanamycin resistance cassette.

Bottom Line: Similar to the regulatory function of this protein in E. coli, five aromatic-pathway genes (aroF-tyrA, aroP, aroL, and tyrP) were significantly reduced upon deletion of the tyrR gene.Interestingly, the acid-stressed genes, hdeB and hdeD, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the tyrR mutant under acidic conditions.In conclusion, regulation of TyrR in Y. pestis is similar to, but distinct from, that in E. coli.

View Article: PubMed Central - PubMed

Affiliation: Department of Sanitary Inspection, School of Public Health, University of South China Hengyang, China ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.

ABSTRACT
Yersinia pestis, 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 Escherichia coli. In this paper, TyrR played an important role in Y. pestis virulence. Inactivation of tyrR did not seem to affect the in vitro 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 tyrR 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 Y. pestis chromosome or plasmids under in vitro growth condition. Similar to the regulatory function of this protein in E. coli, five aromatic-pathway genes (aroF-tyrA, aroP, aroL, and tyrP) were significantly reduced upon deletion of the tyrR gene. Two genes (glnL and glnG) that encode sensory histidine kinase and regulator in a two-component regulatory system involved in nitrogen assimilation were downregulated in the tyrR mutant. Several genes encoding type III secretion proteins were transcribed by 2.0-4.2-fold in a tyrR mutant relative to the WT strain. Interestingly, the acid-stressed genes, hdeB and hdeD, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the tyrR mutant under acidic conditions. In conclusion, regulation of TyrR in Y. pestis is similar to, but distinct from, that in E. coli. TyrR is a metabolic virulence determinant in Y. pestis that is important for extracellular survival and/or proliferation.

No MeSH data available.


Related in: MedlinePlus