Investigating the role of MARTX toxin in cholera-toxin dependent modulation of host innate immune responses during Vibrio cholerae infection.
- Doan, Phillip
- Advisor(s): Rivera-Chavez, Fabian
Abstract
Vibrio cholerae is the bacteria responsible for causing cholera, a diarrheal disease. Cholera affects around 1.3 to 4 million people globally and impacts countries that lack access to sanitary drinking water such as Bangladesh[1]. Given the burden of V. cholerae induced infection, we investigated the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, a secreted toxin. Cholera is typically considered a non-inflammatory disease, and this may be explained by the actions of the MARTX toxin [3]. In this present study, we sought to determine if the MARTX toxin modulated host inflammation to limit bacterial clearance and confer a fitness advantage. Additionally, we wanted to determine whether the actions of MARTX toxin are dependent on V. cholerae’s cholera toxin (CT). We found that genetic abrogation of the MARTX toxin was detrimental to the fitness of the pathogen within the gut of the host. At 6 hours post infection we observed a significant reduction in intestinal colonization by the MARTX toxin mutant, rtxA relative to the wild-type (WT) strain. RT-qPCR data reveal that mice infected with the WT and the mice infected with rtxA have non-significant different expression of intestinal inflammation genes, CXCL1, CXCL2 and Nos-2. However, we report that expression of these inflammation markers was greater in rtxA relative to WT after 6 hours and thus, could explain the observed bacterial enumeration data. These results help elucidate the interaction between bacterial toxins and their impact on host innate immunity, which can be further developed into a more effective cholera vaccine or provide therapeutic targets.