Alternative Pathway to a Glycopeptide-Resistant Cell Wall in the Balhimycin Producer <i>Amycolatopsis balhimycina</i>
Bibliographic record
Abstract
Balhimycin, a vancomycin-type glycopeptide, is a lipid II targeting antibiotic produced by Amycolatopsis balhimycina. A. balhimycina has developed a self-resistance mechanism based on the synergistic action of different enzymes resulting in modified peptidoglycan. The canonical resistance mechanism against glycopeptides is the synthesis of peptidoglycan precursors ending with acyl-d-alanyl-d-lactate (d-Ala-d-Lac) rather than acyl-d-alanyl-d-alanine (d-Ala-d-Ala). This reprogramming is the result of the enzymes VanH, VanA, and VanX. VanH and VanA are required to produce d-Ala-d-Lac; VanX cleaves cytosolic pools of d-Ala-d-Ala, thereby ensuring that peptidoglycan is enriched in d-Ala-d-Lac. In A. balhimycina, the ΔvanHAXAb mutant showed a reduced glycopeptide resistance in comparison to the wild type. Nevertheless, ΔvanHAXAb was paradoxically still able to produce d-Ala-d-Lac containing resistant cell wall precursors suggesting the presence of a novel alternative glycopeptide resistance mechanism. In silico analysis, inactivation studies, and biochemical assays led to the characterization of an enzyme, Ddl1Ab, as a paraloguous chromosomal d-Ala-d-Lac ligase able to complement the function of VanAAb in the ΔvanHAXAb mutant. Furthermore, A. balhimycina harbors a vanYAb gene encoding a d,d-carboxypeptidase. Transcriptional analysis revealed an upregulated expression of vanYAb in the ΔvanHAXAb mutant. VanYAb cleaves the endstanding d-Ala from the pentapeptide precursors, reducing the quantity of sensitive cell wall precursors in the absence of VanXAb. These findings represent an unprecedented coordinated layer of resistance mechanisms in a glycopeptide antibiotic producing bacterium.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".