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MarA-like regulator of multidrug resistance in Yersinia pestis
1Center for Adaptation Genetics and Drug Resistance, Department of Molecular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
Abstract:
MarA47(Yp) from Yersinia pestis, showing 47% identity to Escherichia coli MarA in its N terminus, caused resistance to antibiotics and to organic solvents when expressed in both E. coli and Y. pestis. Resistance was linked to increased expression of the AcrAB multidrug efflux pump. In four of five spontaneous multidrug-resistant mutants of Y. pestis independently selected by growth on tetracycline, the marA47(Yp) gene was overexpressed. The findings suggest that marA47(Yp) is a marA ortholog in Y. pestis.
Insights
The MarA47(Yp) gene from Yersinia pestis confers resistance to antibiotics and solvents by increasing multidrug efflux pump expression. This gene is overexpressed in resistant Y. pestis mutants, suggesting it is a marA ortholog.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- The MarA protein in Escherichia coli regulates genes involved in resistance to various toxic compounds.
- Understanding orthologous genes in other bacterial species can reveal conserved resistance mechanisms.
Purpose of the Study:
- To investigate the function of the Yersinia pestis MarA47(Yp) protein.
- To determine if MarA47(Yp) confers antibiotic and solvent resistance.
- To explore the role of MarA47(Yp) in multidrug resistance in Y. pestis.
Main Methods:
- Gene expression analysis of MarA47(Yp) in E. coli and Y. pestis.
- Phenotypic testing for antibiotic and organic solvent resistance.
- Selection and genetic analysis of spontaneous multidrug-resistant Y. pestis mutants.
Main Results:
- Expression of MarA47(Yp) in E. coli and Y. pestis resulted in resistance to antibiotics and organic solvents.
- This resistance was associated with increased expression of the AcrAB multidrug efflux pump.
- Overexpression of marA47(Yp) was observed in four out of five independently selected multidrug-resistant Y. pestis mutants.
Conclusions:
- MarA47(Yp) functions as a transcriptional activator conferring multidrug resistance in Yersinia pestis.
- The findings strongly suggest that marA47(Yp) is a functional marA ortholog in Y. pestis.
- MarA47(Yp) plays a significant role in the development of spontaneous multidrug resistance in Y. pestis.
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