The conserved σD envelope stress response monitors multiple aspects of envelope integrity in corynebacteria

Area of Science:

• Microbiology
• Bacterial Cell Envelope Biology

Background:

• Mycobacterium species possess a unique and complex cell envelope, crucial for their virulence.
• This envelope includes an outer mycomembrane (MM) layer and a cell wall, contributing to antibiotic resistance.
• Understanding envelope biogenesis is vital for identifying new therapeutic targets against pathogens like Mycobacterium tuberculosis.

Purpose of the Study:

• To investigate the mechanisms governing mycomembrane (MM) biogenesis in Corynebacterium glutamicum.
• To identify genetic factors involved in the proper surface exposure of proteins within the MM.
• To elucidate the role of stress response pathways in maintaining cell envelope integrity.

Main Methods:

• Development of a cell sorting-based screen to identify mutants with defects in porin surface exposure.
• Characterization of the conserved σD envelope stress response pathway.
• Identification of MarP as a site-1 protease activating the σD response.
• Utilizing a reporter system to monitor σD pathway activation in response to envelope biosynthesis defects.

Main Results:

• The conserved σD envelope stress response is essential for porin export to the mycomembrane.
• MarP protease was identified as the activator of the σD pathway by cleaving an anti-sigma factor.
• The σD pathway is induced by defects in both mycolic acid and arabinogalactan biosynthesis.
• This suggests the σD pathway monitors the assembly of distinct cell envelope layers.

Conclusions:

• The σD stress response in C. glutamicum monitors the integrity of multiple cell envelope layers.
• This pathway is activated by signals arising from impaired mycolic acid and arabinogalactan synthesis.
• Members of the σD regulon may play a significant role in protein export to the mycomembrane.
• These findings offer insights into bacterial envelope homeostasis and potential antibiotic targets.