Tau does not protect microtubules during <i>Klebsiella pneumoniae</i> infections
Bibliographic record
Abstract
Hospitals have raised a growing concern for the rampant spread of the bacterial pathogen Klebsiella pneumoniae , which can cause a wide array of symptoms such as pneumonia, urinary tract infections, septicemia, and pyogenic liver abscesses. Moreover, the misuse of antibiotics has contributed to the surge of multidrug‐resistant hypervirulent strains. As a result, therapeutics for K. pneumoniae infections are becoming ineffective leading to lower survival rates and higher mortality rates in highly infected individuals. In our laboratory, we have shown that K. pneumoniae activates katanin microtubule severing enzymes to induce microtubule disassembly in lung epithelial cells. In contrast, microtubule associated proteins (MAPs) in host cells regulate the stability of microtubules and specific MAPs such as Tau (MAPTau) can protect microtubules from katanin‐induced severing. Since Tau plays a role in the stability of microtubules, we hypothesized that Tau protein levels may prevent microtubule disassembly during K. pneumoniae infections. To test this hypothesis, we initially determined if K. pneumoniae targets Tau in infected A549 lung epithelial cells. We lysed uninfected and infected cells and we found that a higher molecular weight Tau species was present in the infected cell lysates. Hyperphosphorylation of Tau typically regulates its binding to microtubules, and thus, we then determined if overexpressing Tau constructs that have different phosphorylation abilities could protect microtubules from K. pneumoniae ‐induced katanin‐mediated severing. To do this, we obtained three green fluorescent protein (EGFP)‐tagged tau constructs: wildtype Tau (wt Tau), hyperphosphorylated Tau (E14 Tau), and Tau that cannot be phosphorylated (AP Tau). We then expressed these plasmids in A549 cells and infected the cells with K. pneumoniae . If Tau protects microtubules from katanin‐severing, E14 Tau should have no effect on K. pneumoniae‐ induced severing while wild‐type Tau and AP Tau should prevent microtubule severing. During these infections no rescue of the microtubule phenotype was observed thus, neither wild‐type Tau nor AP Tau protected microtubules from K. pneumoniae ‐triggered microtubule disassembly. Our findings show that Tau overexpression plays no discernible role in protecting microtubules during Klebsiella pneumoniae infections. Support or Funding Information This study was funded by SFU institutional funds. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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".