Identifying an animal model to study the extracellular role of the bacterial toxin listeriolysin O

Abstract

Listeriolysin O (LLO) is a cholesterol- dependent cytolysin (CDC) secreted by the foodborne, facultative intracellular pathogen Listeria monocytogenes. This toxin is released in the extracellular and intracellular environments, from where it binds to cholesterol on host cell membranes to form pores, facilitating disease development. Among the numerous members of the CDC family, LLO displays unique properties, such as temperature and pH sensitivity. At neutral pH and temperatures above 30°C, LLO undergoes denaturation. The kinetic of LLO inactivation at 37°C (PH 7.4) has not been established. Additionally, a recent study proposed that in comparison to human serum, murine serum highly inactivates another CDC family member, pneumolysin (PLY) produced by the bacterial pathogen Streptococcus pneumoniae. If this toxin-inhibitory property of murine serum also applies to LLO, this would imply that the murine model for L. monocytogenes infection is not appropriate to study the extracellular functions of LLO. The first goal of my work is to establish the kinetic curve model for different concentrations of LLO at 37°C and neutral pH. The second goal is to determine the relative inhibitory activity of sera obtained from various animal species in comparison to human sera in order to establish which animal models would be best to study LLO extracellular activities.