Transposon mutagenesis of «Mycobacterium avium» subsp. «paratuberculosis» to investigate potential pathogenicity islands
Bibliographic record
Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a highly prevalent chronic intestinal disease of cattle. It is also the putative cause of Crohn's disease, a chronic inflammatory bowel disease of humans. The MAP genome contains six segments of DNA called large sequence polymorphisms (LSPP) that are not present in its closest evolutionary relatives and were probably acquired through horizontal gene transfer. Together, they comprise 125kb, or 2.5% of the MAP genome, and contain 96 open reading frames. A detailed analysis of MAP evolution led us to hypothesize that the LSPP are pathogenicity islands, encoding genes important for MAP survival or replication in the host. To test this hypothesis, we generated a 5,000-member transposon-mutant library in MAP K-10 and developed a PCR screening method to identify potential mutants of LSPP genes. We succeeded in isolating a mutant of MAP3776c, which encodes a putative zinc siderophore. It is part of a putative five-gene zinc uptake operon that occupies almost the entirety of the insertion sequence, LSPP15. The MAP3776c mutant does not appear to have in vitro growth defects, and it is able to colonize the livers and spleens of C57Bl/6 mice within one week of intraperitoneal infection. Upcoming data from an ongoing, long-term experiment will determine whether the mutant has altered ability to persist in mice. The mutant of MAP3776c and the transposon-mutant library are useful tools for research on MAP genomics and pathogenicity that might ultimately contribute to improvements in vaccines and immunodiagnostics for Johne's disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".