Peptidoglycan turnover promotes active transport of protein through the bacterial cell wall
Bibliographic record
Abstract
Abstract The bacterial cell wall is a critical load-bearing structure, but is not thought to be an important permeability barrier since proteins freely diffuse through isolated cell wall sacculi and bacteria secrete proteins without the aid of any known channels or transporters in the wall. Using new genetically encoded probes to measure the permeability of the cell in situ at the single-cell level, we discovered that the size threshold determining whether proteins can pass through the Bacillus subtilis sacculus is smaller than was previously thought. We found that transport of small proteins (<10 kDa) through the sacculus was consistent with passive diffusion through discrete pores, while larger proteins (>15 kDa) required the generation of larger pores by inducing peptidoglycan hydrolysis unbalanced by synthesis. These data are consistent with physics-based models of diffusion through a random percolation network of finite thickness. Conversely, the ability of the innate immune factor phospholipase (15.2 kDa) to kill B. subtilis was inhibited by membrane de-polarization. The protective effect of de-polarization was dependent on latent peptidoglycan synthesis (decoupled from cell growth) by PBP1 – highlighting a new role for this enzyme – and on reduced peptidoglycan hydrolysis. These results demonstrate that the rapid peptidoglycan turnover that drives cell growth also promotes movement of phospholipase across the cell wall, identifying a quintessentially bacterial mechanism of active transport. Significance Statement Gram-positive bacteria, which include many serious pathogens like Staphylococcus aureus , Listeria monocytogenes , and Clostridium difficile , are defined by their thick peptidoglycan cell wall. Here, we demonstrate that this structure is a critical permeability barrier that blocks antibacterial proteins like those used by the human innate immune system. Furthermore, this barrier function depends on the physiological state of the cell: the wall of non-growing cells is less permeable because peptidoglycan turnover during growth actively promotes transport of specific proteins through the cell wall. This prokaryotic paradigm for molecular transport has important implications for host-pathogen interactions since pathogenic bacteria often assume both non-growing and growing states during infection.
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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) | 0.001 | 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".