Regulation and function of resistance-nodulation-division efflux pumps in Acinetobacter baumannii ATCC17978 VU
Bibliographic record
Abstract
The loss of effective therapeutic options due to the increase instances of antimicrobial resistant bacterial infections is of great concern to the World Health Organization (WHO). The WHO released a list to prioritize efforts in fighting this problem and placed carbapenem-resistant Acinetobacter baumannii as the top priority in need of development of new therapeutic options. A. baumannii is a Gram-negative opportunistic pathogen that can survive within clinical environments. A lot is known about the ability of this species to resist and tolerate the effects of antimicrobials. It possesses three efflux pumps of the resistance-nodulation-division (RND) efflux family, AdeAB(C), AdeFGH, and AdeIJK, that when overexpressed are responsible for reducing the susceptibility of A. baumannii to several antibiotic classes. These RND efflux pumps, and AdeFGH in particular, were the focus of my study. In this study I have investigated regulation and physiological function of AdeFGH, which is the least well studied RND efflux pump of the three. I have shown that AdeFGH expression has profound effects on the motility and biofilm formation of A. baumannii and that this is most likely due to increased efflux of acyl homoserine lactones. The effect of AdeFGH on motility and biofilm formation appears to be AdeL-independent. Interestingly, the overexpression of AdeL led to increased virulence in Galleria mellonella. I have discovered that the expression of adeFGH is induced by nitrosative stress and regulated by not only its cognate regulator, AdeL, but also by the global regulator, CsrA. I have investigated the role of CsrA in the physiology of A. baumannii via transcriptomics and phenotypic microarray. Additional investigations into AdeIJK showed it was crucial for A. baumannii virulence in G. mellonella and increased expression lead to increased tolerance to osmotic stress. All of this combined furthers our understanding of A. baumannii physiology and identifies several new potential therapeutic targets.
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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".