Translation elongation factor EF-P drives susceptibility to fluoroquinolone antibiotics in Bacillus subtilis

Authors

Ahmed, M., Tollerson, R., Lang, K. S.

Abstract

The emergence of antimicrobial resistance restricts the clinical efficacy of therapeutic antibiotic drugs. Elucidating the molecular mechanisms by which bacteria evade antibiotic activities will lead to novel therapeutic approaches. Therefore, it is critical to understand the mechanisms that govern susceptibility to antibiotics. Fluoroquinolones are a class of antibiotics widely used to treat both Gram-positive and Gram-negative bacterial infections. Resistance to fluoroquinolones is widespread in multiple pathogenic bacteria, limiting their therapeutic usefulness. Resistance to fluoroquinolones is well-known to be mediated by Point mutations in the genes encoding the cellular targets of fluoroquinolones, type-II topoisomerases, leads to clinically relevant resistance. However, several recent studies have revealed that dysregulation of translation influences fitness during fluoroquinolone exposure. For example, several screens have identified insertions in gene that encodes elongation factor P (EF-P) increases survival to fluoroquinolones. Here, we sought to understand the impact of EF-P on fluoroquinolone survival using the Gram-positive model organism Bacillus subtilis. We found that loss of EF-P increases the survival of B. subtilis exposed to fluoroquinolones by several orders of magnitude. Furthermore, we demonstrate that fluoroquinolone sensitivity is dependent on post-translational modification of EF-P, indicating that it is dependent on EF-P activity. Remarkably, loss of EF-P increases survival of cells lacking RecA, a key DNA repair protein, which is crucial for the survival of fluoroquinolone drugs. Using transcriptomics, we identify key cellular response pathways differentially regulated in cells lacking EF-P during fluoroquinolone treatment. We conclude that EF-P regulates diverse mechanisms that drive the susceptibility to fluoroquinolones.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 29 Sep 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.