Structural and mechanistic insights into the transcriptional regulation of chromosomal T6SS by large conjugative plasmid-encoded TetRs in <i>Acinetobacter baumannii</i>
Bibliographic record
Abstract
The type VI secretion system (T6SS) is a highly sophisticated nanomachine widely used by bacteria to achieve competitive advantage, important for survival and pathogenicity. In Acinetobacter baumannii, the large conjugative plasmid pAB3 encodes two TetR-family transcriptional regulators, TetR1 and TetR2, that play crucial roles in restricting T6SS function and promoting recipient survival after conjugation. Using X-ray crystallography, we demonstrate that the plasmid-encoded TetRs are structurally homologous but distinct in DNA sequence binding preferences, which we have also mapped out using chromatin immunoprecipitation and validated with electrophoretic mobility shift assay and isothermal titration calorimetry. Transcriptomics and functional studies demonstrated that TetR1 and TetR2 collaboratively downregulate most of the components of the T6SS, but they also impact metabolic pathways and biofilm formation, having an impact on cell morphology, invasiveness, and virulence in a mouse infection model. Taken together, this work provides structural and mechanistic insights into the widespread regulatory influence of plasmid-encoded TetR1 and TetR2 in A. baumannii, providing new insights into plasmid-chromosome cross-regulating pathways and enlightening antimicrobial drug discovery targeting A. baumannii.
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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 | 0.000 |
| 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".