Elucidating the involvement of catalase in the oxidative stress-induced antibiotic susceptibility, physiology, and virulence of Acinetobacter baumannii
Bibliographic record
Abstract
Acinetobacter baumannii is a Gram-negative opportunistic pathogen that has a high incidence of infection among individuals with compromised immune systems. Currently, 80% of all hospital-acquired A. baumannii infections are multidrug-resistant to at least three different families of antibiotics, including last-line treatments. Therefore, there is an urgent need for effective therapeutic strategies which requires a thorough understanding of bacterial mechanisms of resistance. Infections caused by A. baumannii are difficult to eradicate, not only due to its extensive antibiotic resistance, but also due to its ability to adapt and persist against harsh environmental and host stressors; a prominent one being oxidative stress via the generation of reactive oxygen species (e.g., H2O2). A. baumannii is known to employ protective enzymes such as catalases to degrade hydrogen peroxide to water and oxygen. Mutants with single- and double-deletions of the catalase genes katG and katE, and their respective complements, were subjected to phenotypic assays and omics analysis to help us elucidate the overall contribution of this oxidative stress response in A. baumannii. The catalase mutants exhibited reduced fitness in rich medium, which was exacerbated when supplemented with H2O2. They also displayed differential antibiotic susceptibilities that were presumed to be mediated by the resistance-nodulation-division (RND) efflux pumps. Further assessment of overall efflux activity and expression profile of the RND efflux pump-encoding genes inferred alternative antibiotic resistance mechanism(s), most likely secondary to oxidative stress. Moreover, as H2O2 is generated by the innate immune cells as a pathogen containment and clearing strategy, we were prompted to examine bacterial virulence with a macrophage survivability assay. While the absence of catalases KatG and KatE sensitized A. baumannii to oxidative stress, their involvement in the virulence of this bacterium proved to be complicated. Catalase mutants showed a surprising persistence and possibly adaptive response in phagocytic macrophages. Transcriptomic and genomic sequencing data revealed differential expression of several genes associated with information storage and processing, virulence determinants, and biomolecules transport and metabolism. Together, these observations demonstrated the complex involvement of catalases beyond their primary function of ROS detoxification. Additionally, we also created visualization tools of fluorescence plasmids to aid in the research and study of A. baumannii.
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 | 0.001 |
| 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 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".