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Published on: December 3, 2010
Dimercaptosuccinic acid with membrane-targeting activity against Pseudomonas aeruginosa
Horng-Ren Lo1, Cian-Hui Yan1, Ya Yan2
1Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung, Taiwan.
Background:
Multidrug resistant (MDR) gram-negative bacteria (GNB) are a serious health threat. GNB require divalent cations for the integrity of their outer membrane (OM), which can be inhibited by dimercaptosuccinic acid (DMSA), a sulfhydryl-containing metal chelator that has been used as an antidote to heavy metal toxicity. We aim to investigatethe effects and mechanisms of action of DMSA on Pseudomonas aeruginosa.
Main Methods:
The inhibition of P. aeruginosa strains by DMSA was determined using growth kinetics analysis. Biofilm formation was evaluated using crystal violet staining after incubation for 24 h. We determined the bacterial OM permeability and cell membrane potential using propidium iodide (PI) and bis-(1,3-dibutylbarbituric acid) trimethineoxonol (DiBAC4(3)) staining, respectively, following DMSA exposure. The bioenergetics-related activity of DMSA-treated bacteria was assessed by determining intracellular ATP levels, bacterial motility and N-phenyl-naphtylamide (NPN) efflux assay.
Results:
DMSA inhibited the growth of bacteria in a concentration-dependent manner and repressed biofilm formation by P. aeruginosa. DMSA-treated bacteria exhibited increased PI uptake and enhanced DiBAC4(3) fluorescence intensity compared with untreated cells. Treatment of P. aeruginosa with DMSA reduced the intracellular ATP levels, bacterial motility, and efflux activity in the tested cells.
Significance:
The antibacterial mechanisms of DMSA may be related to alterations in OM permeability, membrane depolarization, and impaired bioenergetics-related activity, which are essential for bacterial viability and infection.
Insights
Dimercaptosuccinic acid (DMSA) inhibits multidrug-resistant Pseudomonas aeruginosa growth and biofilm formation. DMSA disrupts bacterial outer membrane integrity and impairs energy production, offering a potential strategy against gram-negative bacterial infections.
Area of Science:
- Microbiology
- Drug Discovery
- Antimicrobial Resistance
Background:
- Multidrug-resistant gram-negative bacteria (GNB) pose a significant global health threat.
- Outer membrane integrity in GNB relies on divalent cations, presenting a potential target for antimicrobial agents.
- Dimercaptosuccinic acid (DMSA), a metal chelator, has shown potential in disrupting bacterial structures.
Purpose of the Study:
- To investigate the effects of DMSA on Pseudomonas aeruginosa.
- To elucidate the mechanisms of action of DMSA against P. aeruginosa.
Main Methods:
- Growth kinetics analysis to determine bacterial inhibition.
- Crystal violet staining for biofilm formation assessment.
- Propidium iodide (PI) and DiBAC4(3) staining to evaluate outer membrane permeability and cell membrane potential.
- Assays for intracellular ATP levels, bacterial motility, and NPN efflux to assess bioenergetics.
Main Results:
- DMSA demonstrated concentration-dependent inhibition of P. aeruginosa growth and repressed biofilm formation.
- DMSA treatment led to increased PI uptake and enhanced DiBAC4(3) fluorescence, indicating compromised outer membrane and cell membrane potential.
- Intracellular ATP levels, bacterial motility, and efflux activity were significantly reduced in DMSA-treated P. aeruginosa.
Conclusions:
- DMSA exhibits antibacterial activity through mechanisms involving disruption of outer membrane permeability and membrane depolarization.
- Impaired bioenergetics-related activity, including reduced ATP levels and motility, contributes to DMSA's antibacterial effects.
- DMSA presents a promising therapeutic candidate for combating multidrug-resistant gram-negative bacterial infections.
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