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Record W4398219867 · doi:10.1101/2024.05.21.595087

Evolutionary and functional connections between the typhoid toxins encoded by <i>S.</i> Typhi and <i>S. bongori</i>

2024· preprint· en· W4398219867 on OpenAlexaff
Antonio J. Chemello, Casey C. Fowler

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrobial Metabolism and Applications
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsTyphoid feverSalmonella typhiBiologyComputational biologyEvolutionary biologyGeneticsMicrobiologyGene

Abstract

fetched live from OpenAlex

ABSTRACT The virulence properties of numerous important bacterial pathogens have been shaped by the horizontal acquisition of an AB5-type toxin. A major obstacle to the fruitful horizontal transfer of an AB5-type toxin amongst bacteria that infect divergent host species is that these toxins bind specific glycan receptors on target host cells to mediate toxin uptake, and glycosylation patterns vary substantially between different host species. In this study, we explore the evolutionary and functional connections between the related typhoid toxins that are encoded by S. enterica serovar Typhi, a human-adapted pathogen, and by S. bongori , which infects cold-blooded animals. We uncover genetic fingerprints that indicate S . Typhi’s typhoid toxin islet evolved from a larger virulence islet similar to S. bongori ’s, and show that S . Typhi’s glycan-binding PltB subunit is more similar to S. bongori PltB than it is to many diverse PltB sequence variants found in S. enterica . We further show that, surprisingly, S . Typhi strains that encode the S. bongori typhoid toxin islet intoxicate infected human epithelial cells with substantially greater potency than wild-type S . Typhi. The results of this study therefore suggest that the unexpected potency of the S. bongori typhoid toxin toward mammalian cells paved the way for sequence variants derived from this species to be acquired by - and effectively integrated into the virulence program of - the human-adapted pathogen S . Typhi.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.008
GPT teacher head0.202
Teacher spread0.194 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicMicrobial Metabolism and ApplicationsFrench-language works237,207