Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality
Abstract
Understanding the molecular basis of the lethality of antibiotics and certain other stresses is complicated because cell death can result from direct inhibition of a critical biological process as well as from reactive oxygen species (ROS) generated by events metabolically downstream of the direct interaction of the agent with its target. Prior evidence has indicated that the ROS-dependent component of antibiotic lethality is due in part to lethal DNA problems resulting from the incorporation of oxidized nucleotides into DNA and incomplete DNA repair. Our observations unexpectedly indicate that the predominant mechanism of lethality from a hybrid protein that jams the machinery that translocates proteins across the cytoplasmic membrane shares attributes with the ROS-dependent component of antibiotic lethality.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 09, 2017
- Source ID
- 10.1073/pnas.1707466114
Entities
People
- Charley C. Gruber
- Chittampalli N. Yashaswini
- Dana Braff
- Graham C. Walker
- James J. Collins
- Jason H Yang
- Noriko Takahashi
- Sakkarin Bhubhanil
- Silvana Andreescu
- Xiaobo Liu
- Yoshikazu Furuta
Organizations
- Boston University
- Broad Institute
- Chulabhorn Graduate Institute
- Clarkson University
- Defense Threat Reduction Agency
- Harvard University
- Massachusetts Institute of Technology
- National Cancer Institute
- National Institute of Environmental Health Sciences
- National Institute of General Medical Sciences
- National Science Foundation