About

Dr. Christopher A. Rice is an Assistant Professor of Parasitology and Section Head of Microbiology, Immunology and Molecular Genetics at Purdue University's College of Veterinary Medicine. He grew up in Irvine, Ayrshire, Scotland, and developed an early interest in Microbiology during his studies at Ayrshire College. He earned his Bachelor of Science with Honours in Microbiology and Immunology from The University of the West of Scotland (UWS) in 2010, followed by a Ph.D. in 2014 under Dr. Fiona Henriquez-Mui, focusing on histidine and lysine amino acid biosynthesis as antimicrobial targets in Acanthamoeba species. After completing his Ph.D., Dr. Rice moved to the United States for postdoctoral research with Dr. Dennis Kyle at the University of South Florida, where he developed high-throughput drug screening assays targeting Naegleria fowleri and Acanthamoeba species. He continued this work at the University of Georgia (UGA) as part of the Center for Tropical and Emerging Global Diseases, contributing to drug repurposing efforts that identified posaconazole as a combinational therapy for primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri. Dr. Rice expanded his research to include drug discovery for Acanthamoeba spp. and Balamuthia mandrillaris, diversifying beyond Dr. Kyle's focus on N. fowleri. In 2019, Dr. Rice was appointed Assistant Research Scientist and manager of the Center for Drug Discovery at UGA's College of Pharmacy, where he co-developed and lectured in courses on computational and robotic technologies in drug discovery and toxicology. In August 2022, he joined Purdue University as an Assistant Professor, establishing the Rice Research Group. His current research focuses on developing novel diagnostics and drug discovery models for Balamuthia mandrillaris, an emerging and neglected pathogen. Outside of his academic work, Dr. Rice enjoys traveling, socializing, and competitive video gaming.

Research topics

• Virology
• Biology
• Medicine
• Microbiology
• Pharmacology
• Bioinformatics
• Pathology
• Computational biology
• Immunology

Selected publications

• Virulence of <i>Naegleria fowleri</i> isolates varies significantly in the mouse model of primary amoebic meningoencephalitis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-20 · 1 citations

  preprintOpen access

  Abstract Naegleria fowleri is a small free-living amoeba that causes an acute, fatal disease called primary amoebic meningoencephalitis (PAM). One persisting question is why few people succumb to disease when so many are potentially exposed. We tested the hypothesis that N. fowleri isolates vary in virulence and in the minimum infectious dose required to induce disease by using a mouse model of PAM and intranasally inoculating dilutions of five clinical isolates of N. fowleri. Results showed significant differences in onset of severe disease and mortality rates between isolates. Remarkably, for isolate V596, 100 amoebae produced 100% mortality within 5 days. In contrast, higher numbers of amoebae were required for other isolates and mice survived for &gt;2 weeks. Concurrently, we developed an in vitro virulence assay by comparing feeding rates between amoebae isolates seeded onto Vero cells. We observed a positive correlation between cytopathic effects in vitro and virulence in vivo . Article Summary Line Isolates of Naegleria fowleri vary in virulence, which results in significant differences in minimal infectious concentrations of amoebae that cause primary amoebic meningoencephalitis.

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• Cyclic Peptide Natural Product Inspired Inhibitors of the Free-Living Amoeba <i>Balamuthia mandrillaris</i>

  Journal of Natural Products · 2025-02-13 · 2 citations

  articleOpen accessSenior authorCorresponding

  Balamuthia mandrillaris is a pathogenic free-living amoeba (pFLA) that can cause infection of the central nervous system (CNS), called Balamuthia amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with B. mandrillaris have a high mortality rate due to a lack of effective treatments. A nonoptimized antimicrobial drug regimen is typically recommended; however, it has poor antiparasitic activity and can cause various and severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities but are underexplored for their antiamoebic activity. In this study, we evaluated the anti-B. mandrillaris effect of Synthetic Natural Product Inspired Cyclic Peptides (SNaPP) mined from ∼500 biosynthetic gene clusters of various bacterial species. The predicted natural product-43 (pNP-43; BICyP1), identified from the SNaPP library, and its derivates displayed a significant inhibition against B. mandrillaris trophozoites, with five pNPs having IC50s ≤ 5 μM. Furthermore, all hit natural product inspired peptides demonstrated minimal to no hemolytic and cytotoxic effects on human red blood cells (RBCs) and immortalized human carcinoma cells, respectfully. Our study is the first to demonstrate the anti-B. mandrillaris effects of cyclic peptides, offering a promising new direction for drug development.

  PublisherDOI

• Drug susceptibility of a clinical isolate of <i>Balamuthia mandrillaris</i> , a pathogenic free-living amoeba

  Antimicrobial Agents and Chemotherapy · 2025-12-10

  articleOpen access

  ABSTRACT Balamuthia amoebic encephalitis (BAE) is a highly fatal infection caused by Balamuthia mandrillaris , an amoeba that lives in soil and water. In Thailand, three fatal cases of BAE have been documented, but no survivors have been reported, raising questions about current treatment regimens. Previous drug repurposing studies reveal some potent pharmacological compounds, but the drug susceptibility of the clinical isolate of pathogenic amoeba remains variable. Given the success in isolating B. mandrillaris from the human biopsied brain, this study aims to assess the amoebicidal effect of several previously repurposed drugs and suggested therapies for BAE. The trophozoites of a new clinical isolate, the KM-20 strain, were exposed to 12 compounds, including pentamidine, the most widely used antiprotozoal drug, and nitroxoline, the recent radical cure for BAE. The amoebicidal effect was assessed using the ATP level as a cell survival biomarker. The circularity and surface area of the cells were used as recrudescence indicators. Among all drugs tested, nitroxoline is the most potent amoebicidal drug without recrudescence. Topical antiseptic agents caused amoeba lysis at all doses tested, suggesting potential use for cutaneous balamuthiasis. Compared with two laboratory-adapted V039 and PRA-291 strains, the KM-20 isolate had reduced drug susceptibility to all of the tested compounds, suggesting strain dependency of amoebicidal activity. This study provides drug susceptibility data against a novel and geographically diverse clinical isolate of B. mandrillaris to assist in prioritizing anti- Balamuthia agents for further drug development testing, followed by in vivo efficacy testing animal models before clinical trials and drug repurposing.

  PublisherDOI

• Discovery of cyclic peptide natural product inhibitors of <i>Balamuthia mandrillaris</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-05 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Balamuthia mandrillaris is a pathogenic free-living amoeba that causes infection of central nervous system, called Balamuthia amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with B. mandrillaris have a high mortality rate due to the lack of effective treatments. A combination of non-optimized antimicrobial drug regimen is typically recommended; however, they have poor parasite activity and can cause various severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities and lower cytotoxicity. In this study, we evaluated the anti- B. mandrillaris effect of cyclic peptides. The predicted natural product-43 (pNP-43), identified from the SNaPP (Synthetic Natural Product Inspired Cyclic Peptides) library, and its derivates displayed a significant inhibition for B. mandrillaris trophozoites. Eight pNPs had IC 50 s &lt;5 μM. Furthermore, all hit pNPs demonstrated minimal hemolytic and cytotoxic effects on human cells. Our study first indicates the anti- B. mandrillaris effect of cyclic peptides, which provides a new direction for drug development. Further studies of the mechanism of action and in vivo effects will be elucidated to confirm the potency as a treatment for B. mandrillaris infection in the future.

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• Editorial: New advances in the biology and pathogenesis of free-living amoebae

  Frontiers in Microbiology · 2024-04-29 · 4 citations

  editorialOpen accessSenior authorCorresponding

  Free-living amoebae (FLA) are fascinating unicellular eukaryotic microorganisms found worldwide in aquatic and soil habitats. They have an important role in the ecosystems, actively feeding mainly on bacteria and other microorganisms. FLA life cycle is mainly composed of two stages: the trophozoite (the metabolically and replicative form of the amoeba) and the persistent cyst (which is highly resistant to various adverse conditions such as water disinfection processes and therapeutic treatments). While being mainly non-pathogenic, some FLA (namely Acanthamoeba, Naegleria fowleri) are nowadays considered as emerging opportunistic pathogens (Bartrand et al., 2014;Sente et al., 2016). FLA are also well-known reservoirs of amoeba-resistant bacteria (ARB), possibly contributing to the spread of pathogenic ARB (such as Legionella), which constitutes a potential threat to water quality and human health (Samba-Louaka et al., 2019;Chaúque et al., 2022). It is therefore crucial to increase awareness on these neglected waterborne pathogens and related diseases. This special issue presents recent research on several FLA topics and includes studies presented by participants who attended the 19 th international Free-Living Amoeba Meeting held in Poitiers, France, in June of 2023.In this Research Topic, Naegleria fowleri extracellular vesicles (EV) seem of great interest in our community, with two papers by independent lab groups being published. EV characterization and their effect on various clinical isolates of Naegleria fowleri, using SEM methods, or host cells including B103 neuroblastoma or primary cultures of mouse cell microglia were explored by Russell et al., (2023) andRetana Moreira et al., (2024). Staying on theme with N. fowleri, Nadeem et al., (2023) highlight the emerging threat and "outbreak" of N. fowleri in Pakistan. This review highlights the need for improved awareness, public health measures, and water surveillance. Dereeper and co-workers (2023) contributed with six new high-quality Naegleria genomes to establish the Naegleria genus pangenome with a near-tocomplete repertoire of core and accessory genes and highlighting new architecture and functional features in Naegleria.Excitingly, there was a description of one new putative host species of mycobacteria, Rosculus vilicus, within the environment that was published by Jessu and co-workers (2023). This may pose as a potential host and transmission route for Johne's disease and should be kept a closer eye on in the future.A review from Wang et al., (2023) describes the characteristics of Acanthamoeba infection from biological characteristics, classification, disease, and pathogenic mechanism in order to provide scientific basis for the diagnosis, treatment, and prevention of Acanthamoeba infection. Loufouma Mbouaka and co-workers (2023) used Realtime-Glo as a novel 2-D cytotoxicity viability assays being able to monitor the cell health and the pathobiology of Acanthamoeba on feeder cells. This assay could be adapted for Balamuthia pathogenicity models as well, but because Naegleria can also metabolizes the propriety reagent, it may be difficult differentiating between the pathogen or host response in that model.One study assessed the phylogenetic diversity of the mitochondrial genome ribosomal protein S3 (rps3) over 10 strains of B. mandrillaris. Law et al., (2023) propose that due to the copynumber variations (CNVs) and highly variable sequences of the protein tandem repeats of rps3, this could be a perfect target for clinical genotyping assay for B. mandrillaris. 2023) presented a 3-D human neurospheroid model to assess the cytotoxicity and pathobiology response of B. mandrillaris. Using 3-D models, which mimics the human CNS, can provide a more physiologically relevant environment than traditional 2-D cell culture for studying the pathogenicity of amoeba and are particularly useful the reduce experiments using animals models.Sticking to the theme of 3-D models, Campolo and co-workers (2022) describe the aggregation and encystment of Acanthamoeba's response on various contact lens materials under the same conditions. They found that some lenses will promote this aggregation phenotype which will induce a rapid encystment of some Acanthamoeba cells, within a few hours to fully mature cysts, which they believe helps Acanthamoeba to withstand the disinfection process of contact lens care solutions.Lastly, to bring all the amoebae together, Ferrins et al., (2023) describe novel chemical pharmacophores that have various inhibitory activity against Acanthamoeba sp., Naegleria fowleri, or Balamuthia mandrillaris, which have been shown to cross the blood-brain barrier. This exciting physiological property is much needed for the development of any future antiamoebic therapeutics for CNS disease. We cannot just stop at showing just the amoeba inhibitory activity and stating that in vivo pharmacokinetic/pharmacodynamic or in vivo efficacy models need to be performed to "validate the compounds future potential".In conclusion, this Research Topic brings together diverse examples of the ongoing research on FLA regarding (i) FLA biology and pathogenesis (such as Naegleria pangenome or Balamuthia mandrillaris' mitochondrial heterogeneity, the role of extracellular vesicles in N. fowleri-host interaction, (ii) FLA as hosts of zoonotic bacteria (iii) drug development against FLA (namely brain permeable therapeutics against Acanthamoeba, Naegleria, or Balamuthia), various newly described 2-D and 3-D pathobiological models for brain organoid, cytotoxicity, or Acanthamoeba aggregation models and (iv) FLA epidemiology. While this surely represents a glimpse of the ongoing research worldwide, we believe that increased research in disease,

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• Modelling dynamics between free‐living amoebae and bacteria

  Environmental Microbiology · 2024-05-01 · 9 citations

  articleOpen access

  Free-living amoebae (FLA) serve as hosts for a variety of endosymbionts, which are microorganisms that reside and multiply within the FLA. Some of these endosymbionts pose a pathogenic threat to humans, animals, or both. The symbiotic relationship with FLA not only offers these microorganisms protection but also enhances their survival outside their hosts and assists in their dispersal across diverse habitats, thereby escalating disease transmission. This review is intended to offer an exhaustive overview of the existing mathematical models that have been applied to understand the dynamics of FLA, especially concerning their interactions with bacteria. An extensive literature review was conducted across Google Scholar, PubMed, and Scopus databases to identify mathematical models that describe the dynamics of interactions between FLA and bacteria, as published in peer-reviewed scientific journals. The literature search revealed several FLA-bacteria model systems, including Pseudomonas aeruginosa, Pasteurella multocida, and Legionella spp. Although the published mathematical models account for significant system dynamics such as predator-prey relationships and non-linear growth rates, they generally overlook spatial and temporal heterogeneity in environmental conditions, such as temperature, and population diversity. Future mathematical models will need to incorporate these factors to enhance our understanding of FLA-bacteria dynamics and to provide valuable insights for future risk assessment and disease control measures.

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• Latent classes of adverse childhood experiences and adult health and behavioural outcomes in Haiti’s Cité Soleil

  International Journal of Mental Health · 2024-09-18 · 4 citations

  article
  PublisherDOI

• Prevalence and correlates of suicidal ideation in a sample of urban Haiti residents

  International Journal of Mental Health · 2023-09-20 · 1 citations

  articleSenior author

  AbstractThere is a dearth of scientific knowledge regarding suicidal ideation (SI) and adverse childhood experiences (ACEs) in Haiti. We conducted a community survey with a convenience sample of 673 residents from Haiti's Cité Soleil (January - June 2021) to address these gaps. Participants answered questions on SI, on ACEs from the ACE international questionnaire (ACE-IQ) section 5 abuse-related items, on adult experiences of non-partner sexual violence, on use of alcohol to manage stress and on trauma responses. Latent Class Analysis identified a five-class-model of poly-victimization ranging from Class 1 (no abuse) to Class 5 (combination of emotional, physical, and sexual abuse). SI prevalence was 65.3%. Women were nearly twice as likely as men to report SI (95% CI = 1.08–2.74). Class 1 comprised 25% of participants. Class 5 members were almost four times more likely to endorse SI than Class 1 members (95% CI = 1.52–9.10). Class 4 members were roughly four times more likely to endorse SI than Class 1 members. (95% CL = 1.83–7.81). Class 3 members were nearly twice as likely to endorse SI as Class 1 members (95% CI = 1.03–3.35). Participant survivors of NPSV were three times more likely to report SI than non-victims (95% CI = 1.61–5.67). Alcohol use to manage stress increased odds of SI by 1.59 (95% CI = 1.01–2.52). Hypervigilance increased the odds of SI by 3.21 (95% CI = 1.84–5.58). Limitations include recall bias, non-generalizability, use of self-reported data, and ACE-IQ's limitations.Early identification and prevention of SI, ACE, NPSV, alcohol use, and trauma are warranted.Keywords: Haitisuicidal ideationadverse childhood experiencesinterpersonal violencenon-partner sexual violence Disclosure statementNo potential conflict of interest was reported by the author(s)

  PublisherDOI

• Glucose metabolism in the pathogenic free‐living amoebae: Tempting targets for treatment development

  Chemical Biology & Drug Design · 2023-10-20 · 3 citations

  reviewOpen access

  Pathogenic free-living amoebae (pFLA) are single-celled eukaryotes responsible for causing intractable infections with high morbidity and mortality in humans and animals. Current therapeutic approaches include cocktails of antibiotic, antifungal, and antimicrobial compounds. Unfortunately, the efficacy of these can be limited, driving the need for the discovery of new treatments. Pan anti-amebic agents would be ideal; however, identifying these agents has been a challenge, likely due to the limited evolutionary relatedness of the different pFLA. Here, we discuss the potential of targeting amoebae glucose metabolic pathways as the differences between pFLA and humans suggest specific inhibitors could be developed as leads for new therapeutics.

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• Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes

  Frontiers in Microbiology · 2023-05-10 · 4 citations

  articleOpen accessSenior authorCorresponding

  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 (&amp;gt;90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: 2d ( A. castellanii EC 50 : 0.92 ± 0.3 μM; and N. fowleri EC 50 : 0.43 ± 0.13 μM), 1c and 2b ( N. fowleri EC 50 s: &amp;lt;0.63 μM, and 0.3 ± 0.21 μM), and 4b and 7b ( B. mandrillaris EC 50 s: 1.0 ± 0.12 μM, and 1.4 ± 0.17 μM, respectively). With several of these pharmacophores already possessing blood–brain barrier (BBB) permeability properties, or are predicted to penetrate the BBB, these hits present novel starting points for optimization as future treatments for pFLA-caused diseases.

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Recent grants

• Community Partnership/Engagement Core

  NIH · $22.1M · 2019

Frequent coauthors

• Dennis E. Kyle

  University of Georgia

  29 shared

• Claudia Gómez-Liñán

  Instituto de Parasitología y Biomedicina "López - Neyra"

  12 shared

• Wesley C. Van Voorhis

  12 shared

• Guitele J. Rahill

  University of South Florida

  11 shared

• Beatrice L. Colon

  University of Dundee

  11 shared

• Peter J. Myler

  Center for Infectious Disease Research

  10 shared

• Lynn K. Barrett

  10 shared

• Logan Tillery

  Center for Infectious Disease Research

  10 shared

Education

• PhD, Microbiology

  University of the West of Scotland

  2013