Uncovering the Multifaceted Role of PA2649 (nuoN) in Type III Secretion System and Other Virulence Production in Pseudomonas aeruginosa PAO1
Bibliographic record
Abstract
Pseudomonas aeruginosa is a multi-drug-resistant opportunistic pathogen that adapts to challenging environments by deploying virulence factors, including the type III secretion system (T3SS). Emerging evidence points to a role for NADH dehydrogenase complexes in regulating virulence; however, their precise contributions remain unclear. Here, we identify PA2649, a component of the NADH dehydrogenase complex I (nuo operon), as a key regulator of T3SS-related activities. PA2649 deletion resulted in a twofold increase in exoS expression and enhanced cytotoxicity in both A549 cell and Chinese cabbage models. Full revertant of the nuo operon was necessary to restore exoS expression to wild-type levels, suggesting a critical connection between NADH dehydrogenase activity and T3SS regulation. The PA2649 mutation also disrupted the Rsm-Exs regulatory axis, downregulating gacS, rsmY, rsmZ, and hfq while upregulating exsC. Overexpression of rsmY, rsmZ, gacA, hfq, and exsD partially rescued T3SS function, confirming that PA2649 influences T3SS via the Rsm-Exs pathway. Furthermore, PA2649 deletion altered motility, biofilm formation, pyocyanin production, protease activity, and antibiotic susceptibility. These phenotypes could not be complemented with T3SS regulatory genes alone, indicating that PA2649 modulates these traits through mechanisms independent of the Rsm-Exs axis, potentially involving NADH dehydrogenase-associated pathways. This study underscores the multifaceted role of PA2649 in regulating P. aeruginosa pathogenicity and resistance, providing novel insights into its complex regulatory networks and highlighting new avenues for therapeutic targeting.
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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".