Mechanical stimuli activate gene expression via a cell envelope stress sensing pathway

Area of Science:

• Microbiology
• Cell Biology
• Biophysics

Background:

• Mechanosensitive mechanisms regulate tissue repair in eukaryotes.
• The existence of such processes in bacteria remained largely unknown.
• Antibiotic damage in Vibrio cholerae stimulates cell wall synthesis via the VxrAB system.

Purpose of the Study:

• To investigate if mechanical stress alone can activate bacterial mechanosensitive pathways.
• To demonstrate a mechanosensitive gene regulatory system in bacteria.

Main Methods:

• Applied mechanical forces to individual Vibrio cholerae using microfluidics, direct compression, and hydrostatic pressure.
• Monitored VxrAB signaling using a fluorescent protein reporter.
• Assessed VxrAB response in bacteria with reduced cell envelope stiffness (ShyA deletion).

Main Results:

• Increased VxrAB signaling was observed in response to diverse mechanical loading modalities.
• Mechanical stress, independent of antibiotics, was sufficient to activate VxrAB.
• Reduced cell envelope stiffness led to increased deformation and amplified VxrAB signaling.

Conclusions:

• Vibrio cholerae possesses a mechanosensitive gene regulatory system.
• Mechanical signals contribute to the regulation of bacterial cell wall homeostasis.
• This study reveals a novel mechanism for bacterial adaptation to mechanical stress.