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Elucidating the Role of the Naegleria fowleri secretome in a Host-Pathogen Context

Award Number: F31AI197783
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Elucidating the Role of the Naegleria fowleri secretome in a Host-Pathogen Context - Project Summary Naegleria fowleri (Nf), also known as the brain-eating amoeba, is a pathogenic, free-living amoebae that is the causative agent of Primary Amoebic Meningoencephalitis (PAM). Infection occurs when water contaminated with the amoeba enters the nasal passages. The amoeba will then traverse the nasal passages and enter the brain through the olfactory nerves, where it will begin to feed on brain tissue. PAM is a highly fatal disease in humans, with upwards of 97% of infected individuals succumbing to the infection. This high mortality rate highlights a grave need to address issues related to poor treatment outcomes in humans. The major driving factor behind this dire mortality rate is a lack of efficacious drugs that specifically target Nf amoeba. The current drug regimen is a combination therapy of six different drugs, 5 of which are antimicrobials. These drugs are not specific to targeting and killing the amoebae, and their extended use during treatment poses serious toxicities to the infected individual, contributing to the 97% mortality rate in humans. One of the key roadblocks in developing an effective Nf-specific drug is a lack of available drug targets. One potential target for drugs in pathogenic organisms is virulence factors, as they are necessary to induce severe outcomes during infection but are usually not essential to survival. Current research trends have honed in on the secretome of pathogens as excellent drug targets, as these secreted virulence factors are easy to access and highly specific to the pathogen. I have discovered that incubating conditioned media (CM) from highly virulent, feeding Nf amoeba with axenically cultured amoeba drives increased cytopathic effects over mammalian cells. In Aim 1, I will further characterize the secretome mediation of virulent feeding phenotypes. I hypothesize that this phenotype will differ depending on how virulent the Nf isolate’s CM is and what cells the amoeba are feeding over. To do this, I will test whether we see differences using differently virulent Nf isolates and different mammalian cells to fully flesh out the phenotype we see. In addition, I plan to use tandem mass tag Liquid Chromatography-Mass Spectrometry (LC-MS) to identify secreted proteins in the CM that drive this increased feeding phenotype. In Aim 2, I propose to use RNA sequencing to identify changes in the mammalian cells upon exposure to Nf CM. I hypothesize that the secretome is inducing changes in the mammalian cells that the amoebae are sensing, allowing them to start feeding on those cells quicker. This research will take place in Dr. Dennis Kyle’s lab at the University of Georgia (UGA), who is a renowned expert in Plasmodium spp. and Naegleria fowleri drug discovery and host-pathogen interactions, which will allow us to narrow in on optimal secretome drug targets. In addition, UGA is home to the Center for Tropical and Emerging Global Diseases, a distinguished hub that houses one of the largest and most diverse concentrations of parasitologists in the US. Completion of this proposal will enable me to acquire the necessary skills and training in host-parasite interactions and mentorship/leadership to develop into an independent scientist.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	7/28/2026	NEW	$50,114
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	001	1	7/28/2026	NEW	$0
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Elucidating the Role of the Naegleria fowleri secretome in a Host-Pathogen Context

Award Number: F31AI197783

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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