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Journal of Bacteriology, July 2007, p. 4911-4919, Vol. 189, No. 13
0021-9193/07/$08.00+0     doi:10.1128/JB.00451-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Release of the Lipopolysaccharide Deacylase PagL from Latency Compensates for a Lack of Lipopolysaccharide Aminoarabinose Modification-Dependent Resistance to the Antimicrobial Peptide Polymyxin B in Salmonella enterica

Kiyoshi Kawasaki,^1,2* Kotaro China,¹ and Masahiro Nishijima¹

Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo 162-8640,¹ Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyotanabe 610-0395, Japan²

Received 27 March 2007/ Accepted 25 April 2007

Salmonella enterica modifies its lipopolysaccharide (LPS), including the lipid A portion, to adapt to its environments. The lipid A 3-O-deacylase PagL exhibits latency; deacylation of lipid A is not usually observed in vivo despite the expression of PagL, which is under the control of a two-component regulatory system, PhoP-PhoQ. In contrast, PagL is released from latency in pmrA and pmrE mutants, both of which are deficient in aminoarabinose-modified lipid A, although the biological significance of this is not clear. The attachment of aminoarabinose to lipid A decreases the net anionic charge at the membrane's surface and reduces electrostatic repulsion between neighboring LPS molecules, leading to increases in bacterial resistance to cationic antimicrobial peptides, including polymyxin B. Here we examined the effects of the release of PagL from latency on resistance to polymyxin B. The pmrA pagL and pmrE pagL double mutants were more susceptible to polymyxin B than were the parental pmrA and pmrE mutants, respectively. Furthermore, introduction of the PagL expression plasmid into the pmrA pagL double mutant increased the resistance to polymyxin B. In addition, PagL-dependent deacylation of lipid A was observed in a mutant in which lipid A could not be modified with phosphoethanolamine, which partly contributes to the PmrA-dependent resistance to polymyxin B. These results, taken together, suggest that the release of PagL from latency compensates for the loss of resistance to polymyxin B that is due to a lack of other modifications to LPS.

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* Corresponding author. Mailing address: Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kodo, Kyotanabe, Kyoto 610-0395, Japan. Phone: 81-774-65-8588. Fax: 81-774-65-8585. E-mail: kkawasak{at}dwc.doshisha.ac.jp

Published ahead of print on 4 May 2007.

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Journal of Bacteriology, July 2007, p. 4911-4919, Vol. 189, No. 13
0021-9193/07/$08.00+0     doi:10.1128/JB.00451-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Manabe, T., Kawasaki, K. (2008). Extracellular Loops of Lipid A 3-O-Deacylase PagL Are Involved in Recognition of Aminoarabinose-Based Membrane Modifications in Salmonella enterica Serovar Typhimurium. J. Bacteriol. 190: 5597-5606 [Abstract] [Full Text]  
• Murata, T., Tseng, W., Guina, T., Miller, S. I., Nikaido, H. (2007). PhoPQ-Mediated Regulation Produces a More Robust Permeability Barrier in the Outer Membrane of Salmonella enterica Serovar Typhimurium. J. Bacteriol. 189: 7213-7222 [Abstract] [Full Text]