ArticleAntimicrobial agents and chemotherapy2013
Improved efficacy of fosmidomycin against Plasmodium and Mycobacterium species by combination with the cell-penetrating peptide octaarginine.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 57 citations in OpenAlex.
- Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights.Journal of medicinal chemistry · 2025Review
- Detection of intact vancomycin-arginine as the active antibacterial conjugate inRSC medicinal chemistry · 2023Article
- Octaarginine Improves the Efficacy of Nitazoxanide againstPathogens (Basel, Switzerland) · 2022Article
- Apicoplast Journey and Its Essentiality as a Compartment for Malaria Parasite Survival.Frontiers in cellular and infection microbiology · 2022Article
- Isoprenoid alcohols utilization by malaria parasites.Frontiers in chemistry · 2022Article
- Florfenicol-Polyarginine Conjugates Exhibit Promising Antibacterial Activity Against Resistant Strains.Frontiers in chemistry · 2022Article
- A simple and efficient transfection protocol forParasitology · 2020Article
- Enhancing Aqueous Solubility and Antibacterial Activity of Curcumin by Complexing with Cell-Penetrating Octaarginine.ACS omega · 2020Article
- Peptide Probes forACS chemical biology · 2020Article
- Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates.Molecules (Basel, Switzerland) · 2019Article
- Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters.Nature communications · 2019Article
- Prenylquinones in Human Parasitic Protozoa: Biosynthesis, Physiological Functions, and Potential as Chemotherapeutic Targets.Molecules (Basel, Switzerland) · 2019Review
- A Dual-Function Antibiotic-Transporter Conjugate Exhibits Superior Activity in Sterilizing MRSA Biofilms and Killing Persister Cells.Journal of the American Chemical Society · 2018Article
- Cell Penetration, Herbicidal Activity, andHelvetica chimica acta · 2018Article
- Differential activity of methylene blue against erythrocytic and hepatic stages of Plasmodium.Malaria journal · 2018Article
- The Methylerythritol Phosphate Pathway: Promising Drug Targets in the Fight against Tuberculosis.ACS infectious diseases · 2018Review
- Prediction of Cell-Penetrating Potential of Modified Peptides Containing Natural and Chemically Modified Residues.Frontiers in microbiology · 2018Article
- New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium.Frontiers in microbiology · 2016Review
- The Stapled AKAP Disruptor Peptide STAD-2 Displays Antimalarial Activity through a PKA-Independent Mechanism.PloS one · 2015Article
- How do antimalarial drugs reach their intracellular targets?Frontiers in pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. The transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (CPPs), such as oligoarginines. Here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the CPP octaarginine. Fosmidomycin is an antibiotic that inhibits the second reaction in the nonmevalonate pathway of isoprenoid biosynthesis, an essential pathway for many obligate intracellular pathogens, including mycobacteria and apicomplexan parasites. We observed a strict correlation between octaarginine host cell permeability and its ability to improve the efficacy of fosmidomycin. Plasmodium berghei liver-stage parasites were only partially susceptible to an octaarginine-fosmidomycin complex. Similarly, Toxoplasma gondii was only susceptible during the brief extracellular stages. In marked contrast, a salt complex of octaarginine and fosmidomycin greatly enhanced efficacy against blood-stage Plasmodium falciparum. This complex and a covalently linked conjugate of octaarginine and fosmidomycin also reverted resistance of Mycobacteria to fosmidomycin. These findings provide chemical genetic evidence for vital roles of the nonmevalonate pathway of isoprenoid biosynthesis in a number of medically relevant pathogens. Our results warrant further investigation of octaarginine as a delivery vehicle and alternative fosmidomycin formulations for malaria and tuberculosis drug development.
Indexed as
Identifiers
What OpenQuestion holds
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.