PhD Scientific Days 2026

Poster Session 3.U - Molecular Medicine

Persistent Ciprofloxacin Tolerance is Linked to Altered Baseline Transcription in Mycobacterium Smegmatis

Name of the presenter

Döbrőssy, Gergely

Institute/workplace of the presenter

HUN-REN TTK

Authors

Gergely Döbrőssy^1,1, Lilla Fajka^2,3, Angéla Békési^3,4, Dániel Molnár², Beáta G. Vértessy^3,4, Rita Hirmondó⁴, Judit Tóth⁴
1: Molecular Medicine Division, Semmelweis University Doctoral College, Budapest
2: Department of Biochemistry, Eötvös Loránd University, Budapest
3: Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Budapest
4: Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest

Text of the abstract

Introduction
Tuberculosis (TB), caused primarily by Mycobacterium tuberculosis, remains a major global health threat, and the rise of drug-resistant strains continues to challenge TB control efforts. Our earlier work showed that prolonged antibiotic exposure can induce stable phenotypic tolerance in Mycobacterium smegmatis (Msm) without adaptive mutations, although its molecular basis remains unclear [1].

Aims
This study aimed to characterize the transcriptomic programs associated with ciprofloxacin (CIP)-induced phenotypic tolerance in Msm and to investigate the persistence of this tolerance after growth under antibiotic-free conditions.

Methods
Msm cells were conditioned by prolonged exposure to sublethal CIP, while untreated cells served as controls. For transcriptomic analysis, both groups were sampled under baseline conditions and after acute CIP exposure. We performed exploratory transcriptomic comparisons and functional enrichment analyses on samples from the four experimental conditions. To assess the stability of phenotypic tolerance, minimal inhibitory concentration (MIC) assays were conducted on conditioned and control cells grown under antibiotic-free conditions over time.

Results
Comparison of the four transcriptomic profiles showed that acute CIP exposure triggered similar stress responses, characterized by metabolic downshifts and activation of the DNA damage repair pathway, in both groups. However, conditioned cells showed fewer transcriptional changes in stress-related pathways and broader activation of DNA repair functions. MIC assays confirmed that conditioned cells retained elevated CIP tolerance even after two months in antibiotic-free conditions.

Conclusion
Overall, CIP conditioning altered the baseline transcriptional profile, whereas the response to acute stress remained broadly similar. The lasting increase in drug tolerance indicates a stable physiological state that may be sustained by additional regulatory mechanisms, potentially including epigenetic processes.

References
1. Molnár D et al. (2024) eLife, doi:10.7554/eLife.96695.2