A Conserved Regulatory Circuit Controls Large Adhesins in Vibrio cholerae

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Cyclic di-GMP (c-di-GMP) is a key second messenger regulating bacterial biofilm formation and cell attachment.
• Vibrio cholerae, the agent of cholera, utilizes biofilm formation for survival and infectivity, but the underlying regulatory pathways are not fully understood.

Purpose of the Study:

• To characterize a c-di-GMP effector system in Vibrio cholerae that controls adhesin expression and cell surface display.
• To elucidate the structural mechanisms of c-di-GMP receptor-mediated regulation of adhesin proteolysis.
• To identify the physiological roles of c-di-GMP-regulated adhesins in V. cholerae surface attachment and biofilm development.

Main Methods:

• Structural analyses of c-di-GMP receptor and its complex with the second messenger.
• Biochemical assays to determine the functionality of the periplasmic protease.
• Transcriptional and functional assays to assess adhesin roles in V. cholerae.

Main Results:

• An orthologous c-di-GMP effector system regulating two adhesin classes was identified in V. cholerae.
• A conserved autoinhibition mechanism in the c-di-GMP receptor controlling adhesin proteolysis was structurally characterized.
• The periplasmic protease was shown to be functional in cleaving the identified adhesins, and both adhesins were found to be important for surface attachment and biofilm formation.

Conclusions:

• The study defines a conserved and versatile signaling circuit for controlling cell surface adhesin expression in V. cholerae.
• This pathway plays a significant role in V. cholerae biofilm formation and surface attachment.
• Understanding this regulatory circuit may offer targets for controlling V. cholerae adaptability and pathogenicity.