View source for A Single-Cell View of Multiple Antibiotic Resistance in Escherichia coli

By Calin Guet, University of Chicago

'''Nov 4, 2008'''

CNLS Conference room.

:Multiple antibiotic resistance in pathogenic bacteria is one of the main threats to public health.  The multiple antibiotic resistance or ''mar'' phenotype involves several transcriptional regulators that together control influx and efflux of toxic chemical from the cell.  The molecular biology of the ''mar'' phenotype has been studied exclusively at the population level.  Single-cell studies of the gene expression dynamics of genes responsible for ''mar'' are necessary in order to understand cellular variability in resistance to antibiotics.  The ''mar'' operon of ''Escherichia coli'' is constituted of a repressor ''marR'', and an activator gene ''marA''.  ''MarA'' governs the expression of the efflux pump ''AcrAB'' - ''TolC'', the main determinant of multi drug resistance in ''Escherichia coli''.  Using the fluorescent protein ''Venus-YFP'' we monitor in real time the activity of the ''mar'' promoter in single cells across linear micro-colonies.  This approach enables us to construct genealogies of promoter activities across several generations.  We determine the activity of the ''mar'' promoter for different values of the inducer salicylate.  We find that in response to a steady level of inducer, ''mar'' promoter activity is widely heterogeneous across genetically identical daughter cells.  Different promoter activity levels are maintained and inherited over several generations.  We find that heterogeneity in promoter activity varies with inducer level.  The heterogeneous promoter activity phenotype is abolished in a strain that is deleted for the repressor ''MarR''.  Our single-cell approach reveals the presence of non-genetic inheritance patterns in the activity of the ''mar'' promoter.  


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