In Vitro and In Vivo Antibacterial and Antibiofilm Activity of Zinc Sulfate (ZnSO4) and Carvacrol (CV) Alone and in Combination with Antibiotics Against Pseudomonas aeruginosa
Bibliographic record
Abstract
Background/Objectives: Biofilm-embedded bacteria, such as Pseudomonas aeruginosa (P. aeruginosa), are highly resistant to antibiotics, making their treatment challenging. Plant-based natural compounds (PBCs) and metal(loid)-based antimicrobials (MBAs) are promising alternatives. This study evaluated the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and synergistic effects of zinc sulfate (ZnSO4), carvacrol (CV), and antibiotics (ciprofloxacin [CIP], tobramycin [TOB], and azithromycin [AZM]) against P. aeruginosa PAO1. Methods: The MIC and MBC of ZnSO4, CV, and antibiotics were determined using a 96-well plate method. Cytotoxicity was assessed via MTT assay. Fractional inhibitory concentration (FIC), fractional bactericidal concentration (FBC), minimal biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC) indices were calculated for each combination of agents. Checkerboard assays identified interactions, and the effectiveness of combinations was further evaluated in a mouse chronic lung infection model with treatments delivered intratracheally, intraperitoneally, and orally. Results: TOB had the lowest MIC and MBC values, proving most effective against P. aeruginosa PAO1. Strong synergy was observed with CV + ZnSO4 (CV + Zn) combined with CIP, CV with CIP, and CV + Zn with TOB, as indicated by low FIC indices. CV + Zn with TOB and CV with TOB had low FBC indices, while CV + Zn with AZM showed antagonism. In vivo, intratracheal TOB + CV + Zn reduced lung inflammation and tissue involvement, yielding the best histopathological outcomes. The MIC of CIP and TOB was reduced 5-fold and 4-fold, respectively, when combined with CV + Zn. Conclusions: CV + Zn demonstrated strong synergistic effects with antibiotics and effectively managed P. aeruginosa lung infections in mice. These findings highlight its potential as an innovative therapy for biofilm-associated infections.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".