Dennis Kyle Archives - Center for Tropical and Emerging Global Diseases

Discovery of repurposed drugs that disrupt intracellular replication of Burkholderia pseudomallei and Burkholderia mallei and protect against lethal aerosol infection

Donna Huber on September 16, 2026

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are the etiological agents of the fatal diseases melioidosis and glanders, respectively. No licensed vaccine is available to protect against these facultative intracellular bacteria and treatment of infection is difficult, requiring intensive and prolonged antimicrobial therapy with low success rates due to intrinsic resistance of Bp and Bm …

Another host, another mystery: Infection of polychaete Pista palmata (Annelida: Terebellidae) with a new blood fluke (Digenea: Aporocotylidae) in the coastal Northwest Atlantic Ocean

Donna Huber on September 8, 2026

Terebelliform annelids can serve as intermediate hosts for blood flukes of marine fishes and sea turtles. The scarcity of global reports on the life cycles of these parasites reflects the need for further exploration. Our objective was to further our knowledge of the diversity and life cycles of blood flukes in coastal South Carolina (SC), …

In the news: Dennis Kyle

Donna Huber on August 31, 2026

Dennis Kyle, GRA Eminent Scholar in Antiparasitic Drug Discovery and Professor, is quoted in news stories about Naegleria fowleri, aka “brain-eating amoeba”. Rare ‘brain-eating amoeba’ infection leaves North Carolina teen critically ill (WJHL Channel 11 news)

VAMP3 vesicles support host protein recruitment and Plasmodium liver stage development

Donna Huber on August 12, 2026

Plasmodium remodels the host liver cell as an obligatory step in malaria infection. Although several host proteins are recruited to the parasitophorous vacuole membrane (PVM) after invasion, the mechanisms underlying this acquisition remain unknown. Here, we validated the upregulation and recruitment of the host protein CGA during liver stage Plasmodium berghei infection. We then depleted a panel …

Unlocking the potential of ommatins as sustainable photosensitizers for photodynamic therapy

Donna Huber on July 17, 2026

Photodynamic therapy (PDT) has demonstrated efficacy in cancer treatment, with recent advancements concentrating on photosensitizers that generate high levels of reactive oxygen species (ROS) upon light irradiation while exhibiting minimal dark toxicity. In this study, we explored the photophysical properties of ommatins, specifically xanthommatin (Xa), decarboxylated xanthommatin (Dc-Xa), and protected uncyclized xanthommatin (Uc-Xa), and assessed …

Structure-Guided Optimization of Novel Inhibitors of Plasmodium Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites

Donna Huber on June 2, 2026

A fused dihydropyrrolidino-pyrimidine hit with low lipophilicity and excellent ligand efficiency was identified in a biochemical screen of the Global Health Chemical Diversity Library (GHCDL) against Plasmodium lysyl-tRNA synthetase (KRS). Structure-guided lead optimization delivered analogues with potent parasite growth inhibition, excellent biochemical and cellular selectivity (>1000-fold), and oral efficacy in the malaria NOD-scid-IL2Rγnull (SCID) mouse model. Structural …

Characterization of β-Carboline Derivatives Reveals a High Barrier to Resistance and Potent Activity against Ring-Stage and DHA-Induced Dormant Plasmodium falciparum

Donna Huber on October 17, 2025

Malaria, caused by Plasmodium falciparum, remains a major global health challenge, with an estimated 263 million new infections and 597,000 deaths annually. Increasing resistance to current antimalarial drugs underscores the urgent need for new therapeutics that target novel pathways in the parasite. We previously reported a novel class of β-carboline antimalarials, exemplified by PRC1584, which demonstrated …

In the News: Dennis Kyle

Donna Huber on July 3, 2025

Brain-eating amoebas are rare. But hot weather increases the risk (Washington Post) Brain-eating amoeba: Who is most often infected? (Rochester First) (CBS42) (The Hill)

Discovery and optimization of a novel carboxamide scaffold with selective antimalarial activity

Donna Huber on March 28, 2025

Artemisinin combination therapies (ACTs) are critical components of malaria control worldwide. Alarmingly, ACTs have begun to fail, owing to the rise in artemisinin resistance. Thus, there is an urgent need for an expanded set of novel antimalarials to generate new combination therapies. Herein, we have identified a 1,2,4-triazole-containing carboxamide scaffold that, through scaffold hopping efforts, …

Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria

Donna Huber on March 25, 2025

Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers …

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