Regulatory control of temporally expressed integration host factor (IHF) in Legionella pneumophila
Bibliographic record
Abstract
Legionella pneumophila, an intracellular parasite of protozoa, possesses a distinct dimorphic life cycle that alternates between the vegetative replicative form and the resilient but highly infectious cyst form. Previously, temporally expressed heterodimeric integration host factor (IHF) was shown to be required for differentiation into the cyst form. However, the precise regulatory mechanisms controlling the expression of IHF have not been identified. Microplate kinetic assays with GFP reporter promoter fusion constructs in wild-type, Δihf, ΔrpoS and ΔletA mutant strain backgrounds were employed to assess differences in expression levels of ihfA, ihfB, rsmY and rsmZ. Loss of IHF, RsmY and RsmZ expression in various mutant strain backgrounds was confirmed by quantitative PCR. Here we report that the stationary phase sigma factor RpoS is a positive regulator of IHF, whereas IHF appears to act as a positive autoregulator assisting RpoS. Bioinformatic analyses identified a set of IHF binding sites upstream of one RpoS binding site in the promoter region for both ihfA and ihfB. Recombinant IHF protein bound ihfA and ihfB promoter regions in vitro, confirming the functionality of these IHF binding sites that may assist in the bending of the promoter DNA to facilitate transcription activation of ihfA and ihfB by RpoS. Interestingly, the consensus binding site for IHF is very similar to that of the two-component response regulator LetA. LetA negatively regulates transcription of ihfA and ihfB, implying titrational regulatory control by LetA and IHF. Along with LetA, IHF was found to positively regulate expression of the non-coding regulatory RNAs RsmY and RsmZ responsible for the de-repression of CsrA-repressed transcripts associated with cyst formation, and coordinated post-exponential virulent phenotypes. Taken together, these observations indicate that IHF may have more of an integral role in the global regulatory system governing the transition from replicative to cyst forms than previously thought.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".