The involvement of phenylalanine and phenylacetic acid in regulation of pathogenicity in B. cenocepacia K56-2
Bibliographic record
Abstract
Burkholderia cenocepacia is a gram-negative bacterium known for causing persistent lung infections in individuals living with cystic fibrosis. These infections are highly communicable and difficult to treat due to intrinsic and acquired antibiotic resistance. Previously, our research group found that certain steps in the phenylacetic acid (PAA) degradation pathway are required for full pathogenicity of B. cenocepacia in a Caenorhabditis elegans host model. Deleting the paaABCDE operon, which epoxidizes phenylacetyl coenzyme A (PAA-CoA), causes an attenuation in pathogenicity and abolishes exoprotease activity, a virulence marker, in the presence of phenylalanine. However, deleting the previous step in the pathway, the conversion of PAA to PAA-CoA by the paaK ligases, resulted in increased pathogenicity and exoprotease activity. Additionally, deleting cepR, a gene involved in quorum sensing, in ΔpaaK did not abolish exoprotease activity or pathogenicity. I aimed to confirm the phenotype of the ΔpaaKΔcepR and ΔpaaK strains and to further characterize the differences in the ΔpaaABCDE and ΔpaaK strains in phenylalanine and PAA. I discovered that the ΔpaaKΔcepR and ΔpaaK strains likely contain some mutation(s) separate from the PAA degradation pathway that contributes to the presence of pathogenicity. A new ΔcepRΔpaaK strain has abolished exoprotease activity and attenuated pathogenicity, contradictory to previous results. Additionally, new ΔpaaK strains have wild-type (WT) levels of exoprotease activity and pathogenicity. Comparing the ΔpaaABCDE and new ΔpaaK strains, I found that ΔpaaABCDE cannot utilize phenylalanine or PAA as a sole carbon source, while ΔpaaK grows to WT levels on phenylalanine but not PAA. Additionally, ΔpaaABCDE has abolished exoprotease activity in the presence of these metabolites, while ΔpaaK has WT levels of exoprotease activity with phenylalanine but significantly decreased levels in the presence of PAA. These same trends were observed in the slow killing assay with C. elegans when the media was supplemented with phenylalanine or PAA. Untargeted metabolomics was used to further investigate these differences but was unsuccessful in elucidating phenylalanine metabolism in the different strains. These results indicate that both phenylacetyl-CoA and phenylacetic acid are involved in the regulation of pathogenicity in B. cenocepacia K56-2, but the mechanism is still unknown.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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 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".