Investigating The Dynamics In Vibrio Cholerae Pathogenicity By Single-Molecule Palm And Bayesian Statistics

Vibrio cholerae, the species responsible for human cholera, becomes pathogenic upon expression of the cholera toxin and the toxin coregulated pilus. Of particular interest, the key protein for virulence control in V. cholerae is the transmembrane protein TcpP, which remains membrane-bound while binding with specific transcription factors at the chromosomal DNA of the bacterium. Through the use of single-molecule fluorescence microscopy and a Bayesian analysis framework, we accurately elucidate the dynamics of cholera toxin regulation by its upstream promoter TcpP. Furthermore, based on genetic mutations of TcpP and its binding partners, we distinguish precise binding interactions along the pathway to virulence that V.cholerae follows. This mechanistic insight into the regulation of cholera toxin will enable new therapeutics to be developed and, ultimately, the abolition of cholera.