Elucidating bacteria-host interaction mechanisms through MakA in Vibrio cholerae

Recent studies identified MakA, a bacterial secreted protein from Vibrio cholerae, as a lethal factor in both Caenorhabditis elegans and zebrafish, suggesting its role in bacterial pathogenesis. This research focuses on analysis of the role of MakA in interactions between bacteria and host systems.

To achieve this, the project will employ an interdisciplinary approach, leveraging various models such as V. cholerae, C. elegans, cultured cell lines, and in vivo mouse models.

Comprehensive methodologies, including bacterial genetics, mass spectrometry, CRISPR/Cas9 gene editing, high-resolution imaging, lipidomics, and in vivo animal studies, will be used to investigate MakA´s role in bacteria-host interactions and its molecular mechanisms.Specific aims:1.

Analyze the interaction between MakA and mammalian CHRM3, assessing its impact on intestinal colonization and pathogenesis.2. Investigate the role of the CCR2/CCL2 pathway in V. cholerae infection in mammalian systems3.

Dissect the influence of lipid signaling on MakA´s toxicity in C. elegans.With the strong foundational expertise of both host laboratories in V. cholerae research, this proposal is uniquely positioned to achieve significant breakthroughs within a reasonable timeframe.

This study not only aims to advance our understanding of bacterial secreted proteins in disease causation, but also to open avenues for innovative therapeutic strategies against bacterial infections.