Zebrafish Salmonella Infection Models

Introduction

Salmonella infection is caused by Salmonella species, including Salmonella enterica serovars that lead to gastroenteritis, enteric fever, and invasive systemic disease. Typical pathology involves intestinal epithelial invasion, intracellular survival in phagocytes, acute inflammation, and dissemination to systemic tissues in severe cases. Clinical manifestations range from diarrhea, fever, abdominal pain, and vomiting to bacteremia and organ involvement. Infants, older adults, immunocompromised patients, and populations with limited access to safe food and water are at higher risk. Increasing antimicrobial resistance in non-typhoidal Salmonella has further strengthened the need for predictive in vivo infection models.

Current treatment mainly includes supportive care and antibiotics for severe or invasive disease, but drug resistance, intracellular persistence, and host-driven pathology remain major research challenges. Zebrafish Salmonella infection models provide a transparent, genetically tractable vertebrate system for studying bacterial dissemination, macrophage-pathogen interactions, innate immune activation, and anti-infective efficacy in vivo. These models are particularly useful for early-stage antibacterial screening, host-directed therapy evaluation, and mechanistic studies of Salmonella pathogenesis.

Why Zebrafish?

• Real-Time Imaging: Optical transparency enables real-time imaging of fluorescent Salmonella infection.
• Conserved Innate Immunity: Innate immune responses are conserved and active during early larval stages.
• High-Throughput Screening: Small size supports medium- to high-throughput anti-infective drug screening.
• Immune Reporter Lines: Transgenic immune reporter lines allow macrophage and neutrophil tracking in vivo.

Available Zebrafish Disease Models

We provide a spectrum of Salmonella infection models spanning larval systemic and localized infection, immune-cell reporter models, and adult infection:

Phenotypic Evaluation

Key Applications

• Anti-Infective Drug Screening: Anti-infective drug screening for antibacterial compounds active in a living vertebrate host.
• Host-Pathogen Interaction Studies: Host-pathogen interaction studies focusing on macrophage uptake, intracellular survival, and bacterial dissemination.
• Host-Directed Therapy Evaluation: Host-directed therapy evaluation targeting inflammation, autophagy, LC3-associated phagocytosis, or innate immune pathways.
• Pathogenesis Studies: Pathogenesis studies using Salmonella mutants or host genetic backgrounds to define virulence and immune mechanisms.
• In Vivo Efficacy Validation: In vivo efficacy validation of lead compounds before advancing to mammalian infection models.

Study Examples

Zebrafish Larvae as an in vivo Model for Antimicrobial Activity Tests against Intracellular Salmonella. This study established a suitable Salmonella infection model using genetically engineered zebrafish and Salmonella expressing fluorescent proteins (green fluorescent protein GFP and/or mCherry). They detected Salmonella both inside and outside the macrophages of zebrafish larvae. Tetracycline, an antibiotic that cannot penetrate the cell membrane, could eliminate Salmonella located outside the macrophages, but had no effect on the Salmonella inside the macrophages; ceftriaxone was effective in eliminating both types of Salmonella. The results indicated that the zebrafish larval model is helpful for testing the killing effects of various antibacterial drugs on Salmonella inside and outside cells in a complex in vivo environment.

Fig. 1. Infection-model validation (Hauswirth R, Buck J, et al., 2023).

Reference

1. Hauswirth R, Buck J, et al. Zebrafish Larvae as an in vivo Model for Antimicrobial Activity Tests against Intracellular Salmonella. Front. Biosci. (Landmark Ed) 28(5), 99 (2023).