The Omp85 family protein, TamA, exhibits characteristics of a suitable drug target against <i>Pseudomonas aeruginosa</i>
Bibliographic record
Abstract
ABSTRACT The outer membrane (OM) of Gram-negative bacteria is crucial for cell stability and virulence and acts as a permeability barrier. The biogenesis, assembly, and regulation of proteins in the OM are therefore attractive areas of study that could lead to identifying novel drug targets. The Translocation and Assembly Module (TAM), composed of TamA and TamB, facilitates the insertion of some β-barrel proteins into the OM of Escherichia coli and Klebsiella pneumoniae , and has also been implicated in lipid homeostasis. However, its role in Pseudomonas aeruginosa remains mostly uncharacterized. To investigate the TAM’s function and drug target potential in P. aeruginosa , we generated both single- and double-gene TAM knockouts and assessed their fitness using competition growth assays against wild-type (WT) strains. The WT significantly outcompeted the TAM mutants, indicating a fitness defect. Proteomic analysis revealed surprisingly similar profiles between WT and the double knockout strains, while single knockouts showed changes in OM proteins and reduced expression of flagellar components consistent with attenuated swimming motility observed in Δ tamA . Single mutants exhibited differential levels of expression of lipoproteins of the β-barrel assembly machinery suggesting compensatory OM remodelling. In vivo infection assays using Galleria mellonella larvae demonstrated significantly higher survival rates when infected with TAM mutants, with tamA mutants showing the greatest attenuation in virulence. Our findings demonstrate a role the TAM plays in P. aeruginosa virulence and identify TamA as a potential drug target for the development of new antimicrobial therapies. Data summary The RNAseq data reported on in this article are available from ArrayExpress: E-MTAB-15348 The mass spectrometry proteomics data have been deposited to the ProteomeXchange with the dataset identifier PXD06704.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| 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".