 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 24, 2014 |
| Title |
Mycobacterium tuberculosis Lsr2 is a global transcriptional regulator required for adaptation to changing oxygen levels and virulence |
| Platform organisms |
Mycobacterium tuberculosis CDC1551; Mycobacterium tuberculosis H37Rv |
| Sample organism |
Mycobacterium tuberculosis |
| Experiment type |
Expression profiling by array
|
| Summary |
To survive a dynamic host environment, Mycobacterium tuberculosis must endure a series of challenges from reactive oxygen and nitrogen stress, to drastic shifts in oxygen availability. The mycobacterial Lsr2 protein has been implicated in reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2 in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted for lsr2. Analysis of the M. tuberculosis Δlsr2 strain demonstrated that Lsr2 is not required for DNA protection, as this strain was as equally susceptible as the wild-type to DNA-damaging agents. The lsr2 mutant did display severe growth defects under normoxic and hyperoxic conditions, but was not required for growth under low oxygen conditions. However, it was also required for adaptation to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in viability during, as well as a lag in recovery from, anaerobiosis. Gene expression profiling of Δlsr2 under aerobic and anaerobic conditions in conjunction with published DNA binding-site data indicate that Lsr2 is a global transcriptional regulator controlling adaptation to changing oxygen levels. The Δlsr2 strain was capable of establishing an early infection in the Balb/c mouse model; however, it was severely defective in persisting in the lungs and caused no discernible lung pathology. These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection.
|
| |
|
| Overall design |
Wild type H37Rv or lsr2 mutant strains were grown aerobically or in a Rach dormancy model in dubos tween albumin media and analyzed. Alternately, either aerobically grown or Rach model hypoxic samples were challenged with H2O2 samples and harvested 1h later. Experiments were repeated in triplicate or quadruplicate.
|
| |
|
| Contributor(s) |
Bartek I, Voskuil M |
| Citation(s) |
24895305 |
| |
| Submission date |
May 23, 2014 |
| Last update date |
Jul 02, 2014 |
| Contact name |
Martin Voskuil |
| E-mail(s) |
martin.voskuil@ucdenver.edu
|
| Organization name |
CU-AMC
|
| Department |
Microbiology
|
| Street address |
12800 E. 19th Ave. Mail Stop 8333 RC1-North Room P18-9115
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL15398 |
Voskuil Lab Mycobacterium tuberculosis Operon Microarray |
|
| Samples (16)
|
| GSM1398401 |
Aerobic growth, H37Rv vs. lsr2 mutant, replicate 1 |
| GSM1398402 |
Aerobic growth, H37Rv vs. lsr2 mutant, replicate 2 |
| GSM1398403 |
Aerobic growth, H37Rv vs. lsr2 mutant, replicate 3 |
| GSM1398404 |
Aerobic growth, H37Rv vs. lsr2 mutant, replicate 4 |
| GSM1398405 |
24h Rach model, H37Rv vs. lsr2 mutant, replicate 1 |
| GSM1398406 |
24h Rach model, H37Rv vs. lsr2 mutant, replicate 2 |
| GSM1398407 |
24h Rach model, H37Rv vs. lsr2 mutant, replicate 3 |
| GSM1398408 |
48h Rach model, H37Rv vs. lsr2 mutant, replicate 1 |
| GSM1398409 |
48h Rach model, H37Rv vs. lsr2 mutant, replicate 2 |
| GSM1398410 |
48h Rach model, H37Rv vs. lsr2 mutant, replicate 3 |
| GSM1398411 |
Aerobic growth, 3mM H2O2 added, H37Rv vs. lsr2 mutant, replicate 1 |
| GSM1398412 |
Aerobic growth, 3mM H2O2 added, H37Rv vs. lsr2 mutant, replicate 2 |
| GSM1398413 |
Aerobic growth, 3mM H2O2 added, H37Rv vs. lsr2 mutant, replicate 3 |
| GSM1398414 |
48h Rach model, 3mM H2O2 added, H37Rv vs. lsr2 mutant, replicate 1 |
| GSM1398415 |
48h Rach model, 3mM H2O2 added, H37Rv vs. lsr2 mutant, replicate 2 |
| GSM1398416 |
48h Rach model, 3mM H2O2 added, H37Rv vs. lsr2 mutant, replicate 3 |
|
| Relations |
| BioProject |
PRJNA248476 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57948_RAW.tar |
6.7 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...