Fast evolution of SOS-independent multi-drug resistance in bacteria

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Antibiotic resistance is a major public health threat.
• DNA damage and the SOS response are key to resistance against some antibiotics.
• The role of RecA and SOS in β-lactam resistance is not well understood.

Purpose of the Study:

• To investigate the mechanism of rapid β-lactam resistance evolution in *Escherichia coli* lacking RecA.
• To determine if RecA and SOS-mediated mechanisms are involved in β-lactam resistance.

Main Methods:

• Studied ampicillin resistance evolution in RecA-deficient *E. coli*.
• Analyzed DNA repair pathways and reactive oxygen species (ROS) levels.
• Assessed mutation rates and selection pressures.

Main Results:

• RecA-deficient *E. coli* showed rapid, stable ampicillin resistance (20-fold MIC increase in 8 hours).
• Resistance occurred via an SOS-independent mechanism.
• RecA deletion impaired DNA repair, increased ROS, and promoted mutations, with ampicillin selecting for resistant mutants.

Conclusions:

• The repair-redox axis is crucial for bacterial evolvability under antimicrobial stress.
• RecA-deficient bacteria exhibit increased genetic instability and rapid resistance development.
• Antioxidative defense and DNA repair pathways are key targets for understanding antibiotic resistance.