ArticleAntimicrobial agents and chemotherapy2009
Eradication of intracellular Salmonella enterica serovar Typhimurium with a small-molecule, host cell-directed agent.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Novel compounds derived from AR-12 that demonstrate host-directed clearance of intracellularbioRxiv : the preprint server for biology · 2026Article
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- Autophagy is essential for anti-Frontiers in microbiology · 2026Article
- Advancements in understanding tumor-resident bacteria and their application in cancer therapy.Military Medical Research · 2025Review
- Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria.Scientific reports · 2024Article
- MARCKS Inhibition Alters Bovine Neutrophil Responses toBiomedicines · 2024Article
- Chemical modulation of SQSTM1/p62-mediated xenophagy that targets a broad range of pathogenic bacteria.Autophagy · 2022Article
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- A Novel Dibenzoxazepine Attenuates Intracellular Salmonella Typhimurium Oxidative Stress Resistance.Microbiology spectrum · 2021Article
- AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group AInternational journal of molecular sciences · 2021Article
- Overcoming reduced antibiotic susceptibility in intracellular Salmonella enterica serovar Typhimurium using AR-12.FEMS microbiology letters · 2021Article
- Gefitinib Results in Robust Host-Directed Immunity AgainstFrontiers in immunology · 2021Article
- Eating the unknown: Xenophagy and ER-phagy are cytoprotective defenses against pathogens.Experimental cell research · 2020Review
- AR-12 Exhibits Direct and Host-Targeted Antibacterial Activity towardAntimicrobial agents and chemotherapy · 2020Article
- Formulation of host-targeted therapeutics against bacterial infections.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Review
- Heterogeneous Strategies to Eliminate Intracellular Bacterial Pathogens.Frontiers in microbiology · 2020Review
- HIF1A and NFAT5 coordinate NaAutophagy · 2019Article
- Autophagy Induction by a Small Molecule InhibitsAntimicrobial agents and chemotherapy · 2019Article
- Evaluation of synergy between host and pathogen-directed therapies against intracellular Leishmania donovani.International journal for parasitology. Drugs and drug resistance · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Eradication of intracellular pathogenic bacteria with host-directed chemical agents has been an anticipated innovation in the treatment of antibiotic-resistant bacteria. We previously synthesized and characterized a novel small-molecule agent, AR-12, that induces autophagy and inhibits the Akt kinase in cancer cells. As both autophagy and the Akt kinase have been shown recently to play roles in the intracellular survival of several intracellular bacteria, including Salmonella enterica serovar Typhimurium, we investigated the effect of AR-12 on the intracellular survival of Salmonella serovar Typhimurium in macrophages. Our results show that AR-12 induces autophagy in macrophages, as indicated by increased autophagosome formation, and potently inhibits the survival of serovar Typhimurium in macrophages in association with increased colocalization of intracellular bacteria with autophagosomes. Intracellular bacterial growth was partially rescued in the presence of AR-12 by the short hairpin RNA-mediated knockdown of Beclin-1 or Atg7 in macrophages. Moreover, AR-12 inhibits Akt kinase activity in infected macrophages, which we show to be important for its antibacterial effect as the enforced expression of constitutively activated Akt1 in these cells reverses the AR-12-induced inhibition of intracellular serovar Typhimurium survival. Finally, oral administration of AR-12 at 2.5 mg/kg/day to serovar Typhimurium-infected mice reduced hepatic and splenic bacterial burdens and significantly prolonged survival. These findings show that AR-12 represents a proof of principle that the survival of intracellular bacteria can be suppressed by small-molecule agents that target both innate immunity and host cell factors modulated by bacteria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.