Single-Gene Deletion Mutants of Escherichia coli with Altered Sensitivity to Bicyclomycin, an Inhibitor of Transcription Termination Factor Rho

Author:

Tran Lillian1,van Baarsel Joshua A.1,Washburn Robert S.2,Gottesman Max E.23,Miller Jeffrey H.1

Affiliation:

1. Department of Microbiology, Immunology, and Molecular Genetics, and the Molecular Biology Institute, University of California, and the David Geffen School of Medicine, Los Angeles, California 90095

2. Department of Microbiology, Columbia University Medical Center, New York, New York 10032

3. Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York 10032

Abstract

ABSTRACT We have screened the entire KEIO collection of 3,985 single-gene knockouts in Escherichia coli for increased susceptibility or resistance to the antibiotic bicyclomycin (BCM), a potent inhibitor of the transcription termination factor Rho. We also compared the results to those of a recent study we conducted with a large set of antibiotics (A. Liu et al., Antimicrob. Agents Chemother. 54: 1393-1403, 2010). We find that deletions of many different types of genes increase sensitivity to BCM. Some of these are involved in multidrug sensitivity/resistance, whereas others are specific for BCM. Mutations in a number of DNA recombination and repair genes increase BCM sensitivity, indicating that DNA damage leading to single- and double-strand breaks is a downstream effect of Rho inhibition. MDS42, which is deleted for all cryptic prophages and insertion elements (G. Posfai et al., Science 312: 1044-1046, 2006), or W3102 deleted for the rac prophage-encoded kil gene, are partially resistant to BCM (C. J. Cardinale et al., Science 230: 935-938, 2008). Deletion of cryptic prophages also overcomes the increased BCM sensitivity in some but not all mutants examined here. Deletion of the hns gene renders the cell more sensitive to BCM even in the Δ kil or MDS42 background. This suggests that BCM activates additional modes of cell death independent of Kil and that these could provide a target to potentiate BCM killing.

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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