The life cycle of Vibrio cholerae and schematic diagram of V. cholerae attracted by bile in the human body.
February 16, 2016
How vibrio cholera is attracted by bile elucidated
A group of researchers from Osaka University, Hosei University and Nagoya University have revealed the molecular mechanism that Vibrio cholerae, the etiological agent of cholera, is attracted by bile.
(Background)
Cholera, an acute diarrheal disease caused by the infection of the Gram-negative bacterium Vibrio cholerae, remains a global threat to public health. V. cholerae does not produce toxins in nutrient-poor aquatic environments. However, in a nutrient-rich environment, such as the lumen of the human small intestine, it begins to form colonies and expresses pathogenic proteins that cause the serious diarrheal disease. Thus, sensing of environmental chemicals is crucial for pathogenicity of V. cholerae.
V. cholerae is attracted by bile, suggesting that the bacterium senses bile as a chemotactic signal to migrate toward a certain part of intestine. In addition, V. cholerae shows various responses to bile, including synthesis of virulence factors, biofilm formation. Therefore bile-sensing is one of the key properties for its pathogenicity, but it remains unclear how the bacteria sense the bile.
(Results)
We found that V. cholerae is actually attracted by taurine (2-aminoethylsulfonate), a bile component, and that taurine is recognized by a chemotaxis receptor protein, Mlp37. Mlp37 was originally been identified as a chemoreceptor for various proteinogenic amino acids. The structural study of Mlp37 sensor domain in complex with taurine and serine revealed that the ligands bind to the same pocket and that taurine is recognized essentially in the same way as serine. Interestingly, the sensor domain of the ligand complex had a small opening, which would accommodate a larger side chain group, accounting for the broad ligand specificity of Mlp37. This finding has led us to visualize ligand binding to Mlp37 with a fluorescent derivative of serine whose side chain is decorated by a large fluorescent group. We have successfully visualized the ligand binding to the bacterial chemoreceptor as fluorescent spots. This is the first example of the direct detection of the ligand binding to the bacteria chemoreseptor in vivo.
