Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB.

Journal Article (Journal Article)

Bacterial multidrug tolerance is largely responsible for the inability of antibiotics to eradicate infections and is caused by a small population of dormant bacteria called persisters. HipA is a critical Escherichia coli persistence factor that is normally neutralized by HipB, a transcription repressor, which also regulates hipBA expression. Here, we report multiple structures of HipA and a HipA-HipB-DNA complex. HipA has a eukaryotic serine/threonine kinase-like fold and can phosphorylate the translation factor EF-Tu, suggesting a persistence mechanism via cell stasis. The HipA-HipB-DNA structure reveals the HipB-operator binding mechanism, approximately 70 degrees DNA bending, and unexpected HipA-DNA contacts. Dimeric HipB interacts with two HipA molecules to inhibit its kinase activity through sequestration and conformational inactivation. Combined, these studies suggest mechanisms for HipA-mediated persistence and its neutralization by HipB.

Full Text

Duke Authors

Cited Authors

  • Schumacher, MA; Piro, KM; Xu, W; Hansen, S; Lewis, K; Brennan, RG

Published Date

  • January 16, 2009

Published In

Volume / Issue

  • 323 / 5912

Start / End Page

  • 396 - 401

PubMed ID

  • 19150849

Pubmed Central ID

  • PMC2764309

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1163806


  • eng

Conference Location

  • United States