<i>In vitro</i> and <i>in vivo</i> antimicrobial potential of lithium complex against multi-drug resistant <i>Acinetobacter baumannii</i>
Bibliographic record
Abstract
ABSTRACT Acinetobacter baumannii is a Gram-negative pathogen, accountable for lethal nosocomial infections, owing to high pathogenicity and multi-drug resistance (MDR). Hence, the World Health Organization has prioritized this bacterium against which new pharmacophores are required urgently. Therefore, this study evaluates the antimicrobial potential of lithium complex based on salicylic acid, and 1,10-phenanthroline {[Li(phen) 2 sal]} against MDR A. baumannii (MDRAB) through growth inhibition, growth curve assay, biofilm inhibition, and eradication alongside microscopy. The mechanism of action was proposed by flow cytometry and proteomic analysis. Moreover, in vivo efficacy was assessed using an A. baumannii -induced pneumonia model in mice. Results showed that lithium complex significantly inhibited the bacterial growth at 16–32 µg/mL. Growth kinetics revealed that it retarded the bacterial growth after 2–3 h of treatment. Lithium complex significantly inhibited and reduced >70% of biofilms at the MIC level which is a key problem of indwelling and prosthetic devices. Light and atomic force microscopy further indicated disarticulated biofilm and ruptured cellular membrane post-lithium complex treatment. Proteomic analysis revealed that the compound exerted oxidative stress on A. baumannii which may contribute to cell rupturing. Data are available via ProteomeXchange with identifier PXD044293. Flow cytometry confirmed its role in cytoplasmic membrane disintegration. The lithium complex ameliorated the pneumonia symptoms at non-toxic doses of 20 and 40 mg/kg in the pre-clinical A. baumannii -induced pneumonia model as evident by the significant reduction in bacterial burden and parenchymal inflammation. Taken together, these findings suggest that the lithium complex can be a potential drug candidate against MDRAB. IMPORTANCE Multi-drug resistance (MDR) by virtue of evolving resistance and virulence mechanisms among A. baumannii is a global concern which is responsible for lethal hospital-acquired infections. Therefore, it is crucial to develop new therapeutics against it. Metal complexes are compact structures with diverse mechanisms that the pathogens cannot evade easily which make them a strong drug candidate. In this study, we assessed the in vitro and in vivo efficacy of lithium complex {[Li(phen) 2 sal]} against biofilm-forming MDR A. baumannii . The lithium complex displayed strong antimicrobial activity and reduced the pre-formed mature biofilm which is key barrier for antimicrobial action. Moreover, it employs oxidative stress as one of its mode of actions and causes cellular rupturing. Lithium complex was non-toxic and was significantly effective to overcome pneumonia in mice model. These results highlight the untapped potential of metal complexes that can be explored and utilized for combating notorious A. baumannii 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".