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Tag: Dennis Kyle

Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes

Donna Huber on May 10, 2023

Acanthamoeba species, Naegleria fowleri, and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical …

All the pieces matter: UGA researchers collaborate to solve malaria puzzle

Donna Huber on April 25, 2023

Super-resolution microscopy showing malaria parasites infecting human red blood cells. credit: Muthugapatti Kandasamy, Biomedical Microscopy Core They say what doesn’t kill you makes you stronger. Whoever coined that adage had probably never heard of Plasmodium. It’s a microscopic parasite, invisible to the naked eye but common in tropical and subtropical regions throughout the world. Each …

AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes

Donna Huber on January 3, 2023

Malaria, caused by Plasmodium parasites is a severe disease affecting millions of people around the world. Plasmodium undergoes obligatory development and replication in the hepatocytes, before initiating the life-threatening blood-stage of malaria. Although the natural immune responses impeding Plasmodium infection and development in the liver are key to controlling clinical malaria and transmission, those remain relatively unknown. Here we demonstrate that …

Cryopreservation of Plasmodium Sporozoites

Donna Huber on December 7, 2022

Cryopreservation protocol for Plasmodium sporozoites. Malaria is a deadly disease caused by the parasite, Plasmodium, and impacts the lives of millions of people around the world. Following inoculation into mammalian hosts by infected mosquitoes, the sporozoite stage of Plasmodium undergoes obligate development in the liver before infecting erythrocytes and causing clinical malaria. The most promising vaccine candidates for …

Integrative genetic manipulation of Plasmodium cynomolgi reveals MultiDrug Resistance-1 Y976F associated with increased in vitro susceptibility to mefloquine

Donna Huber on December 7, 2022

The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized P. cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resistance marker MDR1 Y976F. Introduction of this mutation using …

Liver-stage fate determination in Plasmodium vivax parasites: Characterization of schizont growth and hypnozoite fating from patient isolates

Donna Huber on September 23, 2022

Plasmodium vivax, one species of parasite causing human malaria, forms a dormant liver stage, termed the hypnozoite, which activate weeks, months or years after the primary infection, causing relapse episodes. Relapses significantly contribute to the vivax malaria burden and are only killed with drugs of the 8-aminoquinoline class, which are contraindicated in many vulnerable populations. …

Streamlining sporozoite isolation from mosquitoes by leveraging the dynamics of migration to the salivary glands

Donna Huber on September 13, 2022

Background: Sporozoites isolated from the salivary glands of Plasmodium-infected mosquitoes are a prerequisite for several basic and pre-clinical applications. Although salivary glands are pooled to maximize sporozoite recovery, insufficient yields pose logistical and analytical hurdles; thus, predicting yields prior to isolation would be valuable. Preceding oocyst densities in the midgut is an obvious candidate. However, it …

Single-cell RNA profiling of Plasmodium vivax-infected hepatocytes reveals parasite- and host- specific transcriptomic signatures and therapeutic targets

Donna Huber on August 25, 2022

The resilience of Plasmodium vivax, the most widely-distributed malaria-causing parasite in humans, is attributed to its ability to produce dormant liver forms known as hypnozoites, which can activate weeks, months, or even years after an initial mosquito bite. The factors underlying hypnozoite formation and activation are poorly understood, as is the parasite's influence on the host …

Direct type I interferon signaling in hepatocytes controls malaria

Donna Huber on July 19, 2022

Malaria is a devastating disease impacting over half of the world's population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has …