Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii

Upmanyu, Kirti; Haq, Qazi Mohd. Rizwanul; Singh, Ruchi

doi:10.3390/antibiotics12071155

Cited by 2 publications

(1 citation statement)

References 53 publications

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“…Resazurin dye was used to determine the biofilm viability at MIC level ( 32 ). Plate was prepared as mentioned in biofilm eradication assay.…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo antimicrobial potential of lithium complex against multi-drug resistant Acinetobacter baumannii

Zehra,

Usmani,

Shafiq

et al. 2023

Microbiol Spectr

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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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“…Resazurin dye was used to determine the biofilm viability at MIC level ( 32 ). Plate was prepared as mentioned in biofilm eradication assay.…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo antimicrobial potential of lithium complex against multi-drug resistant Acinetobacter baumannii

Zehra,

Usmani,

Shafiq

et al. 2023

Microbiol Spectr

View full text Add to dashboard Cite

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Screening of the Pandemic Response Box library identified promising compound candidate drug combinations against extensively drug-resistant Acinetobacter baumannii

Boonyalai,

Peerapongpaisarn,

Thamnurak

et al. 2024

Sci Rep

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Infections caused by antimicrobial-resistant Acinetobacter baumannii pose a significant threat to human health, particularly in the context of hospital-acquired infections. As existing antibiotics lose efficacy against Acinetobacter isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of A. baumannii: A. baumannii 5075, known for its extensive drug resistance, and A. baumannii QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of A. baumannii isolates, with IC50s ≤ 48 µM for A. baumannii QS17-1084 and IC50s ≤ 17 µM for A. baumannii 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both A. baumannii strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant A. baumannii. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.

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Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii

Cited by 2 publications

References 53 publications

In vitro and in vivo antimicrobial potential of lithium complex against multi-drug resistant Acinetobacter baumannii

In vitro and in vivo antimicrobial potential of lithium complex against multi-drug resistant Acinetobacter baumannii

Screening of the Pandemic Response Box library identified promising compound candidate drug combinations against extensively drug-resistant Acinetobacter baumannii

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