RNA polymerase inhibitor activity against Staphylococcus epidermidis biofilms
Bibliographic record
Abstract
Biofilms were defined as the structural phenotype of microbial communities enclosed in the self-produced polymeric matrix mainly composed of extracellular polysaccharides (EPS). S.epidermidis is associated with chronic diseases involving implant medical devices due to its strong ability to form biofilms and they are difficult to eradicate. Rifampin, one of the most active antibiotics used to treat biofilm-associated infections, is a bacterial RNA polymerase (RNAP) inhibitor; however strong bacterial resistance to this drug leads to the need to find more active compounds acting at the same target: bacterial RNAP. In this study, I test whether other bacterial RNAP inhibitors are also active against S.epidermidis biofilms by determining their Minimum Biofilm Eradication Concentration (MBEC) as compared to those of antibiotics functioning through target other than bacterial RNAP (reference antibiotics). Two biofilm assays were used: MBEC P&G assay using Calgary Biofilm device (peg assay) and glass biofilm assay. In the peg assay, biofilm density of 6 log10 of cfu/peg was obtained and used for biofilm susceptibility testing. In addition to Rifampin, three novel synthesized bacterial RNAP inhibitors were found to be more effective in completely eradicate S.epidermidis biofilms in vitro: 3RHTK27, 3RHTK44 and OMTK13 with MBEC value of 25µg/ml, 12.5µg/ml and 50µg/ml, respectively. None of the other antibiotics were able to eradicate S.epidermidis biofilms (MBEC > 400µg/ml). These three RNAP inhibitors were also found to be effective in glass biofilm assay having MBEC values of 6.25µg/ml, 3.125µg/ml and 25µg/ml, respectively. These three compounds are interesting candidates for further development as antibacterial and anti-biofilm agents. Not all RNAP inhibitors which are active against planktonic cells are active against S.epidermidis biofilms. Nevertheless, seeing the same pattern of result from two different assays that reference antibiotics tested were not capable of eradicating biofilms while three out of eleven bacterial RNAP inhibitors tested were active is encouraging and suggesting that RNAP makes a good target for finding drugs to treat biofilm-related diseases.
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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".