The antibacterial activity of a prophage-encoded fitness factor is neutralized by two cognate immunity proteins
Bibliographic record
Abstract
The human gastrointestinal tract is a competitive environment inhabited by dense polymicrobial communities. Bacteroides, a genus of Gram-negative anaerobes, are prominent members of this ecological niche. Bacteroides spp. uses a repertoire of mechanisms to compete for resources within this environment such as the delivery of proteinaceous toxins into neighbouring competitor bacteria and the ability to consume unique metabolites available in the gut. In recent work, Bacteroides stercoris gut colonization was linked to the activity of a prophage-encoded ADP-ribosyltransferase, which was found to stimulate the release of the metabolite inosine from host epithelial cells. This fitness factor, termed Bxa, shares a similar genomic arrangement to bacterial toxins encoded within interbacterial antagonism loci. Here, we report that Bxa also possesses antibacterial ADP-ribosyltransferase activity, raising the question of how Bxa-producing bacteria resist intoxication prior to Bxa's release from cells. To this end, we identify two cognate immunity proteins, Bsi and BAH, that neutralize Bxa's antibacterial activity using distinct mechanisms. BAH acts as an enzymatic immunity protein that reverses Bxa ADP-ribosylation whereas Bsi physically interacts with Bxa and blocks its ADP-ribosylation activity. We also find that the N-terminal domain of Bxa is dispensable for toxicity and homologous domains in other bacteria are fused to a diverse array of predicted toxins found throughout the Bacteroidaceae, suggesting that Bxa belongs to a broader prophage encoded polymorphic toxin system. Overall, this work shows that Bxa is a promiscuous ADP-ribosyltransferase and that B. stercoris possesses mechanisms to protect itself from the toxic activity of this prophage encoded fitness factor.
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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 | 0.001 |
| 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".