Type II toxin/antitoxin MqsR/MqsA controls type V toxin/antitoxin GhoT/GhoS

Area of Science:

• Microbiology
• Molecular Biology
• Bacterial Genetics

Background:

• Toxin/antitoxin (TA) systems regulate bacterial growth and survival.
• Toxin endoribonucleases degrade mRNA, controlling protein synthesis.
• No TA system has been shown to regulate another TA system.

Purpose of the Study:

• To investigate the regulatory relationship between the MqsR/MqsA and GhoT/GhoS TA systems.
• To determine if MqsR influences the stability of ghoT mRNA.
• To elucidate the role of GhoT in bacterial stress response and persistence.

Main Methods:

• In vivo and in vitro mRNA degradation assays.
• Analysis of MqsR cleavage site specificity.
• Genetic manipulation of ghoT mRNA to introduce MqsR cleavage sites.
• Phenotypic analysis of ghost cell formation and cell elongation.

Main Results:

• Toxin MqsR enriches ghoT mRNA by lacking its primary 5'-GCU cleavage site.
• Introduction of MqsR cleavage sites into ghoT mRNA reduces ghost cell formation and cell death.
• GhoT toxin prevents cell elongation under ampicillin stress.
• Under stress, MqsR degrades GhoS antitoxin mRNA, allowing ghoT translation.

Conclusions:

• The GhoT/GhoS TA system is the first identified TA system regulated by another TA system (MqsR/MqsA).
• MqsR-mediated regulation of GhoT/GhoS contributes to bacterial persistence during stress.
• This cross-regulation provides a novel mechanism for controlling bacterial populations.