Regulation of the <scp>KstR</scp>2 regulon of <i><scp>M</scp>ycobacterium tuberculosis</i> by a cholesterol catabolite
Why this work is in the frame
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Bibliographic record
Abstract
Cholesterol catabolism is widespread in actinobacteria and is critical for Mycobacterium tuberculosis (Mtb) virulence. Catabolism of steroid nucleus rings C and D is poorly understood: it is initiated by the CoA thioesterification of 3aα-H-4α(3'-propanoate)-7aβ-methylhexahydro-1,5-indanedione (HIP) by FadD3, whose gene is part of the KstR2 regulon. In Mtb, genes of this regulon were upregulated up to 30- and 22-fold during growth on cholesterol and HIP, respectively, versus another minimal medium. In contrast, genes involved in degrading the cholesterol side-chain and nucleus rings A and B were only upregulated during growth on cholesterol. Similar results were obtained in Rhodococcus jostii RHA1. Moreover, the regulon was not upregulated in a ΔfadD3 mutant unable to produce HIP-CoA. In electrophoretic mobility shift assays, HIP-CoA relieved the binding of KstR2(Mtb) to each of three KstR2 boxes: CoASH, HIP and a related CoA thioester did not. Inspection of the structure of KstR2(RHA1) revealed no obvious HIP-CoA binding pocket. The results establish that Mtb can catabolize the entire cholesterol molecule and that HIP-CoA is an effector of KstR2. They further indicate that KstR2 specifically represses the expression of the HIP degradation genes in actinobacteria, which encode a lower pathway involved in the catabolism of multiple steroids.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it