ArticlePloS one2013
An antimicrobial peptidomimetic induces Mucorales cell death through mitochondria-mediated apoptosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Repositioning Antimicrobial Peptides Against WHO-Priority Fungi.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Commemorating the Landmark Advances in Our Understanding of Mucormycosis by Dimitrios P. Kontoyiannis.Journal of fungi (Basel, Switzerland) · 2025Article
- The Impact of Dimitrios P. Kontoyiannis on Mucormycosis Research.Journal of fungi (Basel, Switzerland) · 2024Article
- Article
- Peptidomimetics in cancer targeting.Molecular medicine (Cambridge, Mass.) · 2022Review
- TLR22-Induced Pro-Apoptotic mtROS Abets UPRFrontiers in immunology · 2022Article
- Mucormycosis Amid COVID-19 Crisis: Pathogenesis, Diagnosis, and Novel Treatment Strategies to Combat the Spread.Frontiers in microbiology · 2021Review
- Induction of apoptosis by an oleanolic acid derivative in SMMC-7721 human hepatocellular carcinoma cells is associated with mitochondrial dysfunction.Oncology letters · 2018Article
- Regulated Forms of Cell Death in Fungi.Frontiers in microbiology · 2017Review
- Statin Concentrations Below the Minimum Inhibitory Concentration Attenuate the Virulence of Rhizopus oryzae.The Journal of infectious diseases · 2016Article
- Article
- Heat shock protein 90 and calcineurin pathway inhibitors enhance the efficacy of triazoles againstMicrobial cell (Graz, Austria) · 2014Article
- Ulinastatin inhibits oxidant-induced endothelial hyperpermeability and apoptotic signaling.International journal of clinical and experimental pathology · 2014Article
- Peptidomimetics as a new generation of antimicrobial agents: current progress.Infection and drug resistance · 2014Review
- New and alternative approaches to tackling antibiotic resistance.F1000prime reports · 2013Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The incidence of mucormycosis has dramatically increased in immunocompromised patients. Moreover, the array of cellular targets whose inhibition results in fungal cell death is rather limited. Mitochondria have been mechanistically identified as central regulators of detoxification and virulence in fungi. Our group has previously designed and developed a proteolytically-resistant peptidomimetic motif D(KLAKLAK)2 with pleiotropic action ranging from targeted (i.e., ligand-directed) activity against cancer and obesity to non-targeted activity against antibiotic resistant gram-negative rods. Here we evaluated whether this non-targeted peptidomimetic motif is active against Mucorales. We show that D(KLAKLAK)2 has marked fungicidal action, inhibits germination, and reduces hyphal viability. We have also observed cellular changes characteristic of apoptosis in D(KLAKLAK)2-treated Mucorales cells. Moreover, the fungicidal activity was directly correlated with vacuolar injury, mitochondrial swelling and mitochondrial membrane depolarization, intracellular reactive oxygen species accumulation (ROS), and increased caspase-like enzymatic activity. Finally, these apoptotic features were prevented by the addition of the ROS scavenger N-acetyl-cysteine indicating mechanistic pathway specificity. Together, these findings indicate that D(KLAKLAK)2 makes Mucorales exquisitely susceptible via mitochondrial injury-induced apoptosis. This prototype may serve as a candidate drug for the development of translational applications against mucormycosis and perhaps other fungal infections.
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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.