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Record W2051147268 · doi:10.13034/cysj-2013-002

The Road to Novel Antibiotics<sup>1</sup>

2013· article· en· W2051147268 on OpenAlexvenueno aff
Sarah Hyslop

Bibliographic record

VenueJournal of Student Science and Technology · 2013
Typearticle
Languageen
FieldEnvironmental Science
TopicPharmaceutical and Antibiotic Environmental Impacts
Canadian institutionsnot available
Fundersnot available
KeywordsAntibioticsKanamycinPseudomonas aeruginosaAntimicrobialMicrobiologyBiologyBacteriaAminoglycosideAntibiotic resistanceGeneGenetics

Abstract

fetched live from OpenAlex

There is an urgent need for novel classes of antibiotics as most species of bacteria have at least one antibiotic resistant gene, resulting in the bacteria being almost impossible to eradicate. In the past 40 years, only two new classes of antibiotics have been developed. It is essential that novel antibiotics be developed to combat the increasing threat from multi-drug resistance bacteria. The purpose of this experiment was to determine if potential novel classes of antibiotics could be identified by analyzing Pseudomonas aeruginosa gene expression in response to 13 antimicrobial substances, these being 9 chemical compounds, 3 plant tinctures, and silver nitrate. The antimicrobial substances and 14 antibiotics were tested against 96 mutated strains of Pseudomonas aeruginosa . Each strain has been mutated to produce light when one specific gene is expressed. This allowed me to determine which genes were affected by each substance. Cluster analyses were run on the results to determine statistically similar patterns of gene expression. The nine antimicrobial chemicals were sorted into two statistically distinct groups from the antibiotics tested. This indicates that they form two potential novel classes of antibiotics, with modes of action distinct from the tested antibiotics. The plant tinctures had methods of action similar to that of Kanamycin, an aminoglycoside, indicating their potential as novel antibiotics. This is a novel experiment as the antimicrobial substances have not previously been analyzed for their genomic effects and the mutant Pseudomonas aeruginosa has not previously been used as an indicator of gene expression. Il y a un besoin alarmant pour de nouvelles classes d’antibiotiques puisque la plupart des espèces de bactéries détiennent au moins un gène de résistance aux antibiotiques, ce qui rend les bactéries presque impossibles à éradiquer. Au cours des quarante dernières années, seulement deux nouvelles classes d’antibiotiques ont été développées. Il est essentiel que de nouveaux antibiotiques soient développés afin de lutter contre la menace croissante de bactéries détenant une résistance pléïotropique (ou ultidrogue). Le but de cette expérience était de déterminer si une nouvelle classe d’antibiotique pouvait être identifiée en analysant l’expression de gène du Pseudomonas aeruginosa en présence de 13 substances antimicrobiennes, soient 9 composés chimiques, 3 teintures de plantes et du nitrate d’argent. Les substances antimicrobiennes et 14 antibiotiques ont été testés contre 96 souches mutées de seudomonas aeruginosa . Chaque souche a été mutée afin de produire de la lumière quand un gène en particulier est exprimé. Ceci m'a permis de déterminer quels gènes sont affectés par chaque substance. Des partitionnements de données ont été effectués sur les résultats pour déterminer des modèles statistiquement similaires d’expression de gènes. Les neuf produits chimiques antimicrobiens ont été classés en deux groupes statistiquement distincts parmi les antibiotiques testés. Cela démontre qu'ils forment deux nouvelles classes d'antibiotiques, avec des modes d’action distincts par rapport aux antibiotiques testés. Les teintures végétales avaient des méthodes d'action similaire à celle de la anamycine, un aminoglycoside, démontrant leur potentiel en tant que nouveaux antibiotiques. Ceci est une nouvelle expérience ingénieuse puisque les substances antimicrobiennes n’avaient pas été analysées auparavant pour leurs effets génomiques et les mutants du Pseudomonas aeruginosa n’avaient pas été auparavant utilisés en tant qu’indicateurs d’expression de gène.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.659
Threshold uncertainty score0.686

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.016
GPT teacher head0.295
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2013
Admission routes1
Has abstractyes

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