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Selective Pressure by Rifampicin Modulates Mutation Rates and Evolutionary Trajectories of Mycobacterial Genomes.

E Cebrián-Sastre¹, A Chiner-Oms², R Torres-Pérez³

¹Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (CNB), CSIC, Madrid, Spain.

Microbiology Spectrum

|July 12, 2023

Summary

This summary is machine-generated.

Increased mutation rates accelerate the development of rifampicin resistance in mycobacteria. A hypermutable strain showed enhanced survival and faster adaptation to this crucial tuberculosis antibiotic.

Keywords:

DNA repair Mycobacterium Mycobacterium smegmatis antibiotic resistance drug resistance evolution evolution experimental evolution mutation mutation accumulation rifampicin

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Area of Science:

Microbiology
Genetics
Evolutionary Biology

Background:

Rifampicin is a critical first-line antibiotic for tuberculosis treatment.
Rising rifampicin resistance poses a significant global health challenge.
Understanding mycobacterial adaptation mechanisms is vital for combating drug resistance.

Purpose of the Study:

To investigate the genomic response of *Mycobacterium smegmatis* to long-term rifampicin exposure.
To analyze mutation accumulation and identify adaptive pathways leading to rifampicin resistance.
To explore the role of hypermutability in antibiotic resistance development.

Main Methods:

Experimental evolution assay with increasing rifampicin concentrations.
Mutation accumulation assay combined with whole-genome sequencing.
Comparative analysis of wild-type and *ΔnucS* mutant strains.

Main Results:

Antibiotic treatment significantly increased the genome-wide mutation rate in wild-type cells.
The hypermutable *ΔnucS* mutant exhibited enhanced survival and accelerated rifampicin resistance.
Multiple evolutionary pathways and adaptive genes contributing to resistance were identified.
Increased mutation rates correlated with higher drug resistance and improved survival.

Conclusions:

Hypermutability can be an adaptive advantage, promoting rapid acquisition of antibiotic resistance.
Rifampicin exposure drives specific genomic changes and diverse evolutionary trajectories towards resistance.
Findings offer insights into preventing drug-resistant mycobacterial infections.