Theses and Dissertations

Advisor

Hanson, Larry

Committee Member

Petrie-Hanson, Lora

Committee Member

Ross, Matthew

Committee Member

Pharr, G. Todd

Date of Degree

8-12-2026

Original embargo terms

Immediate Worldwide Access

Document Type

Dissertation - Open Access

Major

Veterinary & Biomedical Science (Veterinary Medical Research)

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Veterinary Medicine

Department

Department of Comparative Biomedical Sciences

Abstract

Harmful algal blooms are increasing in frequency worldwide, resulting in greater exposure of aquatic organisms to cyanobacterial toxins that threaten fish health and freshwater ecosystems. Although microcystin-LR (MC-LR) and anatoxin-a are well known for their hepatotoxic and neurotoxic effects, respectively, their broader impacts on immune function, cellular metabolism, and host-pathogen interactions remain poorly understood. The objective of this dissertation was to investigate the immunotoxic, metabolic, and molecular effects of MC-LR and anatoxin-a in channel catfish (Ictalurus punctatus) while evaluating the influence of MC-LR on the growth of important bacterial fish pathogens. Channel catfish were exposed to MC-LR or anatoxin-a, and immune responses were evaluated using flow cytometry, extracellular flux analysis, RNA sequencing, and bacterial growth assays. MC-LR significantly altered phagocytic activity and reactive oxygen species and nitrogen species production in the anterior kidney, spleen and posterior kidney, demonstrating tissue- and time-dependent disruption of innate immune function. RNA sequencing of the liver and spleen revealed rapid activation of stress response, immune signaling and cellular communication pathways within 6 hours of exposure, followed by sustained metabolic reprogramming in the liver and persistent immune modulation in the spleen at 24 hours. Mitochondrial stress test further demonstrated tissue-specific bioenergetic responses, with suppressed oxidative phosphorylation and respiratory capacity in liver cells but enhanced respiratory activity in anterior kidney cells. Anatoxin-a similarly disrupted immune function by increasing reactive oxygen species, suppressing bacterially induced reactive nitrogen species production, altering phagocytic responses, and impairing mitochondrial respiration in both liver and kidney cells. MC-LR exhibited limited inhibitory effect on the fish pathogens Aeromonas hydrophila and Edwardsiella piscicida, suggesting that cyanotoxin contamination is unlikely to reduce pathogen persistence during bloom events. Collectively, these findings demonstrate that cyanobacterial toxins disrupt immune function, oxidative balance, mitochondrial bioenergetics, and gene expression in channel catfish, allowing bacterial pathogens to persist in contaminated environments. This work provides a comprehensive understanding of the mechanisms underlying cyanotoxin-induced immunotoxicity and highlights the potential for increased disease susceptibility to fish inhabiting freshwater ecosystems affected by harmful algal blooms.

Sponsorship (Optional)

Agriculture and Food Research Initiative Competitive Grant no. 2019-67016-29917 from the USDA National Institute of Food and Agriculture

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