The Evolution and Sequence Diversity of FhuA in <i>Salmonella</i> and <i>Escherichia</i>
Bibliographic record
Abstract
ABSTRACT The fhuACDB operon, present in a number of Enterobacteriaceae , encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as transporter for physiologically important chelated ferric iron, but also as receptor for various bacteriophages, toxins and antibiotics, which are pathogenic to bacterial cells. In this research, the fhuA gene distribution and sequence diversity were investigated in Enterobacteriaceae , especially Salmonella and Escherichia . Comparative sequence analysis resulted in a fhuA phylogenetic tree that did not match the expected phylogeny based on housekeeping sequence analysis or trees of fhuCDB genes. The fhuA sequences showed a unique mosaic-clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins in Salmonella and Escherichia , among which typical peptide fragment variations could be defined. Six fragmental insertions / deletions and two substitution fragments were discovered, which could well classify the different clusters. Structure modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops of FhuA external pocket. These frequently mutated regions are likely under high selection pressure, and bacterial strains could have escaped from phage infection or toxin / antibiotics attack via fhuA gene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusual fhuA clustering suggests that high frequency exchange of fhuA genes has occurred between enterobacterial strains after distinctive species were established. IMPORTANCE The enterobacterial fhuACDB operon encodes proteins which mediate the uptake of siderophores to supply the cells with iron essential for bacterial survival. Here we show different evolutionary patterns for the fhu genes within the same operon. The fhuA has a phylogenetic tree that does not match the species phylogeny, whereas the rest of the fhu genes do. The fhuA genes showed inter-species sequence convergence and conservation within specific serovars and serotypes. Nearly all of the significant sequence differences among FhuA clusters are located in potential ligand-binding sites on the extracellular surface of fhuA-encoding receptors. The unusual fhuA clustering suggests the frequent recombination and exchange of fhuA genes between enterobacterial strains in the evolutionary state after distinctive species were established. Our findings suggested either a new evolutionary mechanism or local gene recombination in fhuA that is in contrast to previous evolutionary hypotheses that have formed under the assumption of no recombination.
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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 | 0.001 | 0.001 |
| 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) | 0.000 | 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 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".