Related Experiment Video
Updated: Oct 3, 2025
Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
The Error-Prone Polymerase DnaE2 Mediates the Evolution of Antibiotic Resistance in Persister Mycobacterial Cells
S Salini1, Sinchana G Bhat1, Saba Naz2
1Mycobacterium Research Laboratory, Rajiv Gandhi Centre for Biotechnologygrid.418917.2, Thiruvananthapuram, Kerala, India.
Abstract:
Applying antibiotics to susceptible bacterial cultures generates a minor population of persisters that remain susceptible to antibiotics but can endure them for extended periods. Recent reports suggest that antibiotic persisters (APs) of mycobacteria experience oxidative stress and develop resistance upon treatment with lethal doses of ciprofloxacin or rifampicin. However, the mechanisms driving the de novo emergence of resistance remained unclear. Here, we show that mycobacterial APs activate the SOS response, resulting in the upregulation of the error-prone DNA polymerase DnaE2. The sustained expression of dnaE2 in APs led to mutagenesis across the genome and resulted in the rapid evolution of resistance to antibiotics. Inhibition of RecA by suramin, an anti-Trypanosoma drug, reduced the rate of conversion of persisters to resistors in a diverse group of bacteria. Our study highlights suramin's novel application as a broad-spectrum agent in combating the development of drug resistance.
Insights
Bacterial persisters develop antibiotic resistance by activating the SOS response and upregulating error-prone DNA polymerase DnaE2. The drug suramin inhibits this process, offering a new strategy against bacterial drug resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Discovery
Background:
- Antibiotic treatment generates persister cells that survive antibiotic exposure.
- Mycobacterial persisters develop resistance via unknown mechanisms, possibly involving oxidative stress.
Purpose of the Study:
- To elucidate the mechanisms of de novo resistance emergence in mycobacterial persisters.
- To identify potential therapeutic targets for combating antibiotic resistance development.
Main Methods:
- Analysis of SOS response activation in mycobacterial persisters.
- Investigating the role of DNA polymerase DnaE2 in mutagenesis and resistance.
- Testing the efficacy of RecA inhibition by suramin in various bacterial species.
Main Results:
- Mycobacterial persisters activate the SOS response, leading to DnaE2 upregulation.
- Sustained DnaE2 expression drives mutagenesis and rapid antibiotic resistance evolution.
- Suramin inhibits RecA, reducing persister-to-resistor conversion across diverse bacteria.
Conclusions:
- The SOS response and DnaE2 are key drivers of antibiotic resistance in bacterial persisters.
- Suramin demonstrates potential as a broad-spectrum agent to prevent drug resistance development.
Related Concept Videos
01:30Development of Antibiotic Resistance
00:57Antibiotic Selection
02:10Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
02:46Genome Copying Errors
01:36Mismatch Repair
01:31Proofreading
Errors During Replication are Corrected by the DNA Polymerase...