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Journal of Bacteriology, February 2006, p. 1180-1183, Vol. 188, No. 3
0021-9193/06/$08.00+0     doi:10.1128/JB.188.3.1180-1183.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A pmrA Constitutive Mutant Sensitizes Escherichia coli to Deoxycholic Acid

Jamie M. Froelich, Khoa Tran, and Daniel Wall*

Anadys Pharmaceuticals, Inc., San Diego, Calif

Received 22 August 2005/ Accepted 10 November 2005

An Escherichia coli mutant was isolated and shown to be polymyxin B resistant. Mapping and sequence analysis revealed a missense mutation at codon 53 within the pmrA (basR) gene that results in a G-to-V substitution. Fusions of promoters from the pmrC, yibD, and pmrH genes with the lacZ reporter showed that they were constitutively expressed in pmrA53 cells. In pmrA+ strains, these promoters were induced by iron and zinc, while a {Delta}pmrA mutation blocked induction. The PmrA regulon regulates genes whose products remodel the composition and charge of lipid A and hence the barrier properties of the outer membrane. Along these lines, the pmrA53 mutant was also found to be hypersensitive to the anionic bile detergent deoxycholic acid.


* Corresponding author. Mailing address: Department of Microbiology, Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121. Phone: (858) 530-3711. Fax: (858) 530-3644. E-mail: dwall{at}anadyspharma.com.


Journal of Bacteriology, February 2006, p. 1180-1183, Vol. 188, No. 3
0021-9193/06/$08.00+0     doi:10.1128/JB.188.3.1180-1183.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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