Pathogenic bacteria experience pervasive RNA polymerase backtracking during infection.

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Eukaryotic host defenses can inflict DNA damage on pathogens, disrupting essential molecular processes like transcription.
• Stalled RNA polymerase (RNAP) due to DNA damage can increase mutagenesis, potentially impacting pathogen evolution.
• Understanding how host-induced stress affects transcription machinery dynamics is crucial for deciphering bacterial infection.

Purpose of the Study:

• To investigate the dynamics of RNAP movement and chromosomal association in *Salmonella enterica* during host infection.
• To determine the genome-wide impact of host defense mechanisms on bacterial transcription.
• To identify the role of RNAP dynamics and associated factors in bacterial pathogenesis.

Main Methods:

• Development of a novel methodology to track RNAP dynamics in *Salmonella enterica* during infection.
• Genome-wide analysis of RNAP movement and association with the bacterial chromosome.
• Investigation of the function of anti-backtracking factors in relation to RNAP dynamics.

Main Results:

• RNAP movement dynamics significantly change across the bacterial chromosome during infection.
• Pervasive RNAP backtracking is observed on the *Salmonella* chromosome during infection.
• Anti-backtracking factors are identified as critical for bacterial pathogenesis.

Conclusions:

• Host environments can unexpectedly promote antimicrobial resistance and hypervirulence in pathogens.
• Stalled RNAPs accelerate bacterial evolution through increased mutagenesis.
• Targeting RNAP dynamics presents a potential strategy to combat bacterial infections.