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Journal of Bacteriology, July 2009, p. 4441-4450, Vol. 191, No. 13
0021-9193/09/$08.00+0     doi:10.1128/JB.01474-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

SoxRS-Mediated Lipopolysaccharide Modification Enhances Resistance against Multiple Drugs in Escherichia coli{triangledown}

Joon-Hee Lee,1* Kang-Lok Lee,2 Won-Sik Yeo,2 Su-Jin Park,1 and Jung-Hye Roe2

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, South Korea,1 Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea2

Received 20 October 2008/ Accepted 11 April 2009

Lipopolysaccharide (LPS) is a major constituent of the outer membrane of gram-negative bacteria that serves as a barrier against harmful molecules, including antibiotics. The waaYZ locus that encodes the LPS core biosynthetic function in Escherichia coli was found to be induced strongly by superoxide generators but not by H2O2, ethanol, or heat shock. This induction was dependent on SoxRS, a superoxide and nitric oxide sensing system, through a soxbox in the waaY promoter that binds SoxS. A {Delta}waaYZ mutant became more sensitive to some superoxide generators, and the activation of SoxR by these drugs became more sensitized in the mutant. Through phenotypic microarray analysis, we found that the mutant became sensitive to a wide variety of chemicals not restricted to oxidizing agents. We found that the mutant is under envelope stress and is altered in LPS composition, as monitored by the level of {sigma}E activation and changes in the electrophoretic mobility of LPS, respectively. waaY expression was also regulated by MarA (multiple-antibiotic resistance regulator), which shares a binding site (soxbox) with SoxS, and was induced by salicylate, a nonoxidative compound. These results demonstrate a novel way of protecting gram-negative bacteria against various compounds by modifying LPS, possibly through phosphorylation. Since either oxidant or nonoxidant compounds elicit resistance toward themselves and other toxic drugs, this mechanism could serve as an efficient way for pathogenic bacteria to enhance survival during antibiotic treatment within an oxidant-rich host immune environment.

* Corresponding author. Mailing address: Laboratory of Microbiology, Department of Pharmacy, College of Pharmacy, Pusan National University, Research Building 532, San 30, Jangjun-Dong, Geumjung-Gu, Busan 609-735, South Korea. Phone: 82-051-510-2821. Fax: 82-051-513-6754. E-mail: joonhee{at}pusan.ac.kr

{triangledown} Published ahead of print on 17 April 2009.

Journal of Bacteriology, July 2009, p. 4441-4450, Vol. 191, No. 13
0021-9193/09/$08.00+0     doi:10.1128/JB.01474-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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