Salmonella and the oxidative burst : tales of a complicated relationship.
Bibliographic record
Abstract
Salmonella is one of the most abundant bacterial pathogens infecting humans in developed and developing countries. It is the causative agent of disease and mortality resulting in billions of dollars in associated medical costs and lost productivity every year. In the laboratory, findings regarding the physiology of Salmonella infections are often used to model a wide range of bacterial infections impacting fields far beyond the scope of Salmonella pathogenesis alone. For these reasons, significant resources have been dedicated to gaining a better understanding of mechanisms underlying Salmonella infection and the interaction between the pathogen and the immune system. In this thesis, Salmonella is used to study the interaction between bacterial pathogens and the host’s oxidative and nitrosative burst. Recently, new findings have challenged the conventional perspective of reactive oxygen and nitrogen species as merely antimicrobial agents by revealing redox-sensitive virulence mechanisms that benefit Salmonella infection. These new findings, together with processes that drive Salmonella infection, are highlighted in Chapter 1. To better address questions concerning redox stress inside bacteria we used redox-sensitive GFP which enabled real-time analysis of the intra-bacterial redox environment. In Chapter 2 this redox-biosensor combined with high-throughput microscopy, was used to evaluate oxidative/nitrosative stress evasion strategies inside macrophages. In Chapter 3, the same method was used to explore the bacterial outer membrane permeability to hydrogen peroxide. Real-time measurements of the intra-bacterial redox potential revealed novel regulatory mechanisms that alter outer membrane permeability based on the presence or absence of reactive oxygen and nitrogen species. Chapter 4 describes the identification and characterization of a redox-sensitive regulatory modification in Salmonella effector SteB. This modification was found to be crucial for regulation of tubulin-mediated transport of the Salmonella containing vacuole. Cumulatively these studies describe strategies for oxidative/nitrosative stress evasion while also highlighting several mechanisms by which reactive oxygen and nitrogen species aid Salmonella during infection. In Chapter 5, these findings have been integrated in order to gain a more comprehensive understanding of the complicated relationship between Salmonella and oxidative/nitrosative stress which has the potential to lead to the development of novel antimicrobial therapies.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".