Dimercaptosuccinic acid with membrane-targeting activity against Pseudomonas aeruginosa

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis Pub Date : 2025-04-05 DOI:10.1016/j.micpath.2025.107550

Horng-Ren Lo , Cian-Hui Yan , Ya Yan , Chung-Cheng Lo

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引用次数: 0

Abstract

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.

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来源期刊

Microbial pathogenesis 医学-免疫学

CiteScore

7.40

自引率

2.60%

发文量

472

审稿时长

56 days

期刊介绍： Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)