Title

A novel in vivo model to study bacterial pathogenesis and screen potential therapeutic targets.

Document Type

Article

Department

Biological and Biomedical Sciences

Abstract

As insects rely for their protection against infection on an entirely innate immune system, the use of an insect model is particularly relevant in the study of human newborn Escherichia coli K1 meningitis, the control of which has significant dependency on the innate immune system. Using an in vivo model of neuropathogenic E. coli meningitis, it is shown that immunization with E. coli K-12 can protect locusts against subsequent challenge of invasive E. coli K1. Immunization with other microbes such as Staphylococcus aureus and Acanthamoeba spp. had no effect on K1-induced locust mortality, suggesting immune specificity in invertebrates. The locust immune system was capable of memory and mounting protection against subsequent challenge with invasive K1 for up to 5 days. The usefulness of locusts for the assessment in vivo of potential therapeutic agents was tested. Gentamicin protected locusts against E. coli K1- and S. aureus-mediated death. These finding suggest that the simple locust model described in the present study has the scope in exploring the efficacy of novel drugs (testing large chemical libraries) in microbial diseases, allowing inexpensive, rapid, and even high-throughput experimentation and has no legislative restrictions. Future studies will determine bacterial antigenic determinants and how innate memory functions in locusts. A complete understanding of how locusts' innate immune cells (i.e., haemocytes) respond robustly and specifically against bacterial pathogens will be crucial for the control of neonatal E. coli infection by limiting the ability of the bacteria to overwhelm the host immune system in the early stages of infection.

Publication

Journal of Medical Microbiology