Transferrin binding in <i>Staphylococcus aureus</i>: involvement of a cell wall‐anchored protein
Bibliographic record
Abstract
The ability to gain access to iron is pivotal for bacterial pathogens during infection. Although much is known about iron acquisition systems in Gram-negative bacteria, comparatively little is known about how Gram-positive pathogens access iron from host iron sources. A previous study showed that, in the Gram-positive human pathogen Staphylococcus aureus, a cell surface-associated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) enzyme (Gap, or Tpn) is capable of binding human transferrin, representing a potential means by which this bacterium is able to access iron in vivo. We have investigated this property of S. aureus further and shown that, in S. aureus RN6390, GAPDH is expressed on the S. aureus cell surface independent of exogenous iron concentrations, and that overexpressed and purified Gap, although retaining GAPDH activity, has no affinity for human transferrin. Moreover, although a S. aureus gap mutant was devoid of surface-associated and cytoplasmic GAPDH activity, it retained the ability to bind human transferrin, equivalent to wild type. We concluded from these results that the Gap protein is not involved in S. aureus binding to human transferrin. We identified the transferrin-binding protein as a novel cell wall-anchored protein, designated StbA for staphylococcal transferrin-binding protein A, which shared no significant similarities with any other bacterial transferrin-binding proteins. StbA contained a C-terminal cell wall-anchoring motif (LPKTG), and expression of StbA in the cell wall was strictly controlled by exogenous iron concentrations. The stbA gene is found within a 7 kb region in the S. aureus chromosome that contains a total of six iron-regulated genes. Immediately downstream from stbA is an iron-regulated gene whose product was predicted to be another cell wall-anchored protein with no significant similarity to proteins with characterized functions. Transcribed in the opposite direction from stbA is a four-gene operon whose expression is also regulated by iron. While the deduced products of the first two genes lack similarity to known proteins, the last two genes encode, respectively, putative lipoprotein and permease components of an ABC transporter that shares significant similarities with several iron(III) ABC transporters in a variety of bacteria.
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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 | 0.000 |
| 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".