 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 04, 2021 |
| Title |
Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice |
| Organism |
Mycobacterium tuberculosis H37Rv |
| Experiment type |
Other
|
| Summary |
The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the heterogeneous immune response of the host. Understanding this interplay has proven difficult, largely because experimentally tractable small animal models do not recapitulate the heterogenous disease observed in natural infections. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to associate bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and represent reproducible models of qualitatively distinct immune states. Global analysis of Mtb mutant fitness across the CC panel revealed that a large fraction of the pathogen’s genome is necessary for adaptation to specific host microenvironments. Both immunological and bacterial traits were associated with genetic variants distributed across the mouse genome, elucidating the complex genetic landscape that underlies host-pathogen interactions in a diverse population.
|
| |
|
| Overall design |
Subject mice (48 Collaborative Cross strains, 8 Collaborative Cross parents, 4 k/o strains) were infected via tail vein injection with a saturated M. tuberculosis himar1 transposon library. Animals were sacrificed after 4 weeks, or earlier if moribund, and Tn-Seq was performed after library recovery from harvested spleens. In the majority of cases, two replicates were obtained per mouse strain, 6 replicates in the case of in vitro-grown libraries.
|
| |
|
| Contributor(s) |
Smith CM, Baker RE, Proulx MK, Mishra BB, Long JE, Park SW, Lee H, Kiritsy MC, Bellerose MM, Olive AJ, Murphy KC, Papavinasasundaram K, Boehm FJ, Reames CJ, Meade RK, Hampton BK, Linnertz CL, Shaw GD, Hock P, Bell TA, Ehrt S, Schnappinger D, de Villena FP, Ferris MT, Ioerger TR, Sassetti CM |
| Citation(s) |
35112666 |
| |
| Submission date |
Jan 03, 2021 |
| Last update date |
Feb 23, 2022 |
| Contact name |
Richard E Baker |
| E-mail(s) |
richard.baker@umassmed.edu
|
| Phone |
508-856-6046
|
| Organization name |
University of Massachusetts Medical School
|
| Department |
Microbiology & Physiological Systems
|
| Street address |
55 Lake Avenue North
|
| City |
Worcester |
| State/province |
MA |
| ZIP/Postal code |
01655 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL20677 |
Illumina HiSeq 2500 (Mycobacterium tuberculosis H37Rv) |
|
| Samples (123)
|
|
| Relations |
| BioProject |
PRJNA689305 |
| SRA |
SRP300088 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164156_RAW.tar |
34.3 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE164156_output_bg.tab.gz |
9.1 Mb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...