Understanding Vibrio cholerae Pathogenesis: Insights From Bile Acid Metabolism and Microbial Interactions
Year: 2024
Type: dissertation
Abstract: Vibrio cholerae is a Gram-negative bacterium responsible for cholera, a highly contagious diarrheal disease posing a significant global public health threat, particularly in developing countries. To successfully colonize and cause disease in the host, V. cholerae must travel through the stomach's harsh conditions and withstand fluctuations in oxygen levels, pH, and encounter bile and antimicrobial peptides in the intestines. Bile acids, prominent components of bile, play pivotal roles in regulating V. cholerae's virulence gene expression and influencing disease progression. Bacterial bile salt hydrolases (BSH) facilitate bile acid modification by cleaving amino acids from bile acid molecules, thereby altering the composition of bile acid pool.In this study, we identified a novel Vibrio Bile Salt Hydrolase (VBH) capable of deconjugating taurodeoxycholic acid (TDCA) to deoxycholic acid (DCA) and converting taurochenodeoxycholic acid (TCDCA) to chenodeoxycholic acid (CDCA). Our findings demonstrate that VBH activity influences V. cholerae growth and colonization dynamics, as well as interactions with other gut microbes such as Blautia obeum through bile acid processing. Additionally, we uncovered a novel regulatory pathway where autoinducer-2 (AI-2) modulates secondary bile acid metabolism in Clostridium scindens, highlighting bile acids' broader impact on gut commensals. Furthermore, we explored how V. cholerae's disease outcomes are shaped by interactions with gut commensals, their ability to degrade mucin, and induce mucin production. Lastly, we propose the application of single-cell RNA sequencing (scRANseq) techniques to deepen our understanding of host-microbe interactions involving V. cholerae. These insights promise to inform novel therapeutic strategies combating V. cholerae infections and other enteric diseases.
Author: Ge, Siyi
Institution: University of California, Riverside
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6997169210