Discovery of Biofilm-Inhibiting Compounds to Enhance Antibiotic Effectiveness Against M. abscessus Infections DOI Creative Commons

Elizaveta Dzalamidze,

Mylene Gorzynski,

Rebecca Vande Voorde

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 225 - 225

Опубликована: Фев. 7, 2025

Background/Objectives: Mycobacterium abscessus (MAB) is a highly resilient pathogen that causes difficult-to-treat pulmonary infections, particularly in individuals with cystic fibrosis (CF) and other underlying conditions. Its ability to form robust biofilms within the CF lung environment major factor contributing its resistance antibiotics evasion of host immune response, making conventional treatments largely ineffective. These biofilms, encased an extracellular matrix, enhance drug tolerance facilitate metabolic adaptations hypoxic conditions, driving bacteria into persistent, non-replicative state further exacerbates antimicrobial resistance. Treatment options remain limited, multidrug regimens showing low success rates, highlighting urgent need for more effective therapeutic strategies. Methods: In this study, we employed artificial sputum media simulate conducted high-throughput screening 24,000 compounds from diverse chemical libraries identify inhibitors MAB biofilm formation, using Crystal Violet (CV) assay. Results: The screen established 17 hits ≥30% inhibitory activity mycobacteria. Six these inhibited formation by over 60%, disrupted ≥40%, significantly impaired bacterial viability as confirmed reduced CFU counts. conformational assays, select showed potent formed clinical isolates both avium subsp. hominissuis (MAH). Key compounds, including ethacridine, phenothiazine, fluorene derivatives, demonstrated against pre- post-biofilm enhanced antibiotic efficacy, intracellular loads macrophages. Conclusions: This study results underscore potential target biofilm-associated mechanisms, them valuable candidates use adjuncts existing therapies. findings also emphasize investigations, initiation medicinal chemistry campaign leverage structure–activity relationship studies optimize biological underexplored class nontuberculous mycobacterial (NTM) strains.

Язык: Английский

Discovery of Biofilm-Inhibiting Compounds to Enhance Antibiotic Effectiveness Against M. abscessus Infections DOI Creative Commons

Elizaveta Dzalamidze,

Mylene Gorzynski,

Rebecca Vande Voorde

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 225 - 225

Опубликована: Фев. 7, 2025

Background/Objectives: Mycobacterium abscessus (MAB) is a highly resilient pathogen that causes difficult-to-treat pulmonary infections, particularly in individuals with cystic fibrosis (CF) and other underlying conditions. Its ability to form robust biofilms within the CF lung environment major factor contributing its resistance antibiotics evasion of host immune response, making conventional treatments largely ineffective. These biofilms, encased an extracellular matrix, enhance drug tolerance facilitate metabolic adaptations hypoxic conditions, driving bacteria into persistent, non-replicative state further exacerbates antimicrobial resistance. Treatment options remain limited, multidrug regimens showing low success rates, highlighting urgent need for more effective therapeutic strategies. Methods: In this study, we employed artificial sputum media simulate conducted high-throughput screening 24,000 compounds from diverse chemical libraries identify inhibitors MAB biofilm formation, using Crystal Violet (CV) assay. Results: The screen established 17 hits ≥30% inhibitory activity mycobacteria. Six these inhibited formation by over 60%, disrupted ≥40%, significantly impaired bacterial viability as confirmed reduced CFU counts. conformational assays, select showed potent formed clinical isolates both avium subsp. hominissuis (MAH). Key compounds, including ethacridine, phenothiazine, fluorene derivatives, demonstrated against pre- post-biofilm enhanced antibiotic efficacy, intracellular loads macrophages. Conclusions: This study results underscore potential target biofilm-associated mechanisms, them valuable candidates use adjuncts existing therapies. findings also emphasize investigations, initiation medicinal chemistry campaign leverage structure–activity relationship studies optimize biological underexplored class nontuberculous mycobacterial (NTM) strains.

Язык: Английский

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