Heterogeneity in efflux pump expression predisposes antibiotic-resistant cells to mutation
Imane El Meouche1,2, Mary J Dunlop3,2
1Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA 02215, USA.
Science (New York, N.Y.)
|November 10, 2018
Summary
Transient antibiotic resistance, driven by multidrug efflux pumps, can increase mutation rates. This suggests temporary bacterial evasion strategies may lead to permanent genetic changes and antibiotic resistance.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Antibiotic resistance is a growing public health threat.
- Bacteria can develop temporary resistance through mechanisms like multidrug efflux pumps.
- The link between transient resistance and the promotion of permanent genetic mutations remains unclear.
Purpose of the Study:
- To investigate whether transient antibiotic resistance can promote permanent genetic changes in bacteria.
- To explore the role of the multidrug pump AcrAB-TolC in this process.
Main Methods:
- Utilized time-lapse microscopy to observe bacterial behavior.
- Analyzed the expression of the multidrug pump AcrAB-TolC and the DNA mismatch repair gene MutS.
- Quantified mutation frequencies in bacterial populations.
Main Results:
- Higher expression of the AcrAB-TolC pump correlated with lower expression of the MutS gene.
- Elevated AcrAB-TolC expression was associated with reduced bacterial growth rates.
- Increased mutation frequencies were observed in cells with higher AcrAB-TolC expression.
Conclusions:
- Transient antibiotic resistance mediated by elevated AcrAB-TolC expression can foster spontaneous mutations.
- This mechanism highlights how temporary bacterial evasion strategies may drive the evolution of permanent antibiotic resistance.
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