Exploring Metalloproteome Remodeling in Calprotectin-Stressed <i>Acinetobacter baumannii</i> Using Chemoproteomics
Bibliographic record
Abstract
The growth of bacterial pathogens is limited by nutritional immunity, where the infected host deploys transition metal scavenging proteins including calprotectin (CP) to starve the bacterium of essential transition metals. Prior work reveals that CP induces a significant Zn- and Fe-starvation response in the Gram-negative opportunistic pathogen Acinetobacter baumannii in liquid culture. Here, we employ a quantitative chemoproteomics platform to pinpoint changes in abundance-corrected cysteine reactivity─and by extension cellular metal occupancy in metalloenzymes─that occur when A. baumannii is challenged with physiological CP in liquid culture relative to an untreated WT control. Changes in protein abundance with CP stress reveal a pronounced Zn-limitation and Fe-starvation response and reciprocal regulation of three enzymes of central carbon metabolism, including aconitase. A majority of the 2645 quantifiable Cys-containing peptides that show an increase in abundance-corrected Cys reactivity (150) are derived from known Zn-, Fe-, and Fe–S-cluster proteins, revealing a significant decrease in metal occupancy (undermetalation) across the proteome. Myriad cell processes are impacted by undermetalation, including enzymes that function in the TCA cycle and respiration, GTP metabolism, ribosome remodeling, tRNA charging, and proteostasis. In an effort to identify an undemetalated client enzyme for the candidate GTPase-powered metallochaperone ZigA, we performed this chemoproteomics experiment in a CP-stressed Δ zigA strain relative the CP-stressed wild-type strain. These findings reveal that the loss of ZigA is effectively silent in this assay. We conclude that CP induces a widespread, negative impact on the metalation status of the metalloproteome that results in a significant nutrient limitation response.
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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 | 0.001 |
| Research integrity | 0.001 | 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".