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| Status |
Public on Apr 04, 2018 |
| Title |
A novel hybrid two-component system Lvr mediates virulence and global regulation in pathogenic Leptospira |
| Organism |
Leptospira interrogans serovar Manilae |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Transmission of leptospirosis requires that the spirochete pathogen adapts rapidly to the mammalian host milieu during infection and the external environment upon shedding from the renal tubules of animal reservoirs. The pathogenic Leptospira genomes encode a notably large number (≥76) of putative two-component system (TCS) proteins, which presumably play a key role in switching the ecological niches. Yet to date, the regulatory networks that govern virulence and environmental adaptation have not been elucidated in Leptospira. We identified seven ORFs encoding putative TCS proteins that are exclusively conserved in all the pathogenic Leptospira species. Two of these ORFs (LMANv2_670020, LMANv2_670019), juxtaposed in an operon, are predicted to encode a cytoplasmic hybrid histidine kinase and response regulator. Corresponding transposon mutants ΔlvrA/B and ΔlvrB demonstrated a loss-of-virulence in a hamster model of leptospirosis and aberrant motility phenotype. RNA sequencing revealed the differential expression of transcripts on a global scale in ΔlvrA/B (8.13%), ΔlvrB (5.06%) and ΔlvrA/B∩ΔlvrB (8.24%). In vitro transcriptomes provided insights into the role of Lvr dyad in regulating virulence, motility, signal transduction and metabolism related genes. Phosphotransfer assays indicated that LvrA interacts with LvrB in a branched signaling pathway. Phylogenetic analyses indicated that Our findings suggest that a novel, hybrid two-component system Lvr plays a key role in governing virulence and mediating global regulation in pathogenic Leptospira.
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| |
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| Overall design |
To study the impact of two transposon mutants in signal transduction genes in Leptospira and study their role in virulence.
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| Contributor(s) |
Adhikarla H, Wunder E, Ko A |
| Citation(s) |
29600195 |
| Submission date |
Mar 11, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Sameet Mehta |
| E-mail(s) |
sameet.mehta@yale.edu
|
| Organization name |
Yale University
|
| Street address |
300 Cedar St.
|
| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06520-8327 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21582 |
Illumina HiSeq 2500 (Leptospira interrogans serovar Manilae) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA314958 |
| SRA |
SRP071655 |
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