ArticleThe Journal of antimicrobial chemotherapy2025
Indolocarbazoles as host-directed therapeutics against intracellular infections by methicillin-resistant Staphylococcus aureus.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Next-generation anti-infective drugs in the post-antibiotic era: focusing on anti-virulence agents targeting the bacterial quorum sensing system.Frontiers in cellular and infection microbiology · 2026Review
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Authors and funding
5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesMethicillin-resistant Staphylococcus aureus (MRSA) is a principal contributor to mortality and morbidity attributable to antimicrobial resistance. Many MRSA strains are able to invade host cells, thereby further evading antibiotic treatment. Previously, indolocarbazole GW296115X was identified as a hit compound with host-directed activity against intracellular MRSA. This study evaluates the efficacy and selectivity of indolocarbazoles as potential host-directed therapy against intracellular MRSA. Furthermore, we assessed the interaction between indolocarbazoles and standard-of-care antibiotics.
methodsBioluminescent luxBADCE-expressing MRSA was used to evaluate antimicrobial activity in planktonic cultures and HeLa cell intracellular infection models. Drug safety was assessed through lactate dehydrogenase (LDH) release and WST-1 cytotoxicity assays. The interaction between selected indolocarbazoles in combination with vancomycin or daptomycin was determined based on the Bliss independence model.
resultsIndolocarbazoles GW296115X, staurosporine aglycone, CDK4 inhibitor and SB-218078 showed activity against intracellular MRSA with SB-218078 demonstrating the best potency. None of the effective compounds impaired host cell viability, although host cell metabolic activity was affected to various extents. Combining SB-218078 or GW296115X with vancomycin or daptomycin synergistically eradicated both intracellular and extracellular MRSA.
conclusionsIndolocarbazoles, particularly GW296115X and SB-218078, enhance standard antibiotic efficacy against invasive MRSA and offer potential for host-directed therapy.
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