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Title: A divergent Pseudomonas aeruginosa palmitoyltransferase essential for cystic fibrosis-specific lipid A
Authors: Iyarit Thaipisuttikul
Lauren E. Hittle
Ramesh Chandra
Daniel Zangari
Charneal L. Dixon
Teresa A. Garrett
David A. Rasko
Nandini Dasgupta
Samuel M. Moskowitz
Lars Malmström
David R. Goodlett
Samuel I. Miller
Russell E. Bishop
Robert K. Ernst
University of Maryland, Baltimore
Mahidol University
McMaster University, Faculty of Health Sciences
Vassar College
Massachusetts General Hospital
Harvard Medical School
ETH Zurich
University of Maryland School of Pharmacy
University of Washington, Seattle
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 1-Jan-2014
Citation: Molecular Microbiology. Vol.91, No.1 (2014), 158-174
Abstract: Strains of Pseudomonas aeruginosa (PA) isolated from the airways of cystic fibrosis patients constitutively add palmitate to lipid A, the membrane anchor of lipopolysaccharide. The PhoPQ regulated enzyme PagP is responsible for the transfer of palmitate from outer membrane phospholipids to lipid A. This enzyme had previously been identified in many pathogenic Gram-negative bacteria, but in PA had remained elusive, despite abundant evidence that its lipid A contains palmitate. Using a combined genetic and biochemical approach, we identified PA1343 as the PA gene encoding PagP. Although PA1343 lacks obvious primary structural similarity with known PagP enzymes, the β-barrel tertiary structure with an interior hydrocarbon ruler appears to be conserved. PA PagP transfers palmitate to the 3′ position of lipid A, in contrast to the 2 position seen with the enterobacterial PagP. Palmitoylated PA lipid A alters host innate immune responses, including increased resistance to some antimicrobial peptides and an elevated pro-inflammatory response, consistent with the synthesis of a hexa-acylated structure preferentially recognized by the TLR4/MD2 complex. Palmitoylation commonly confers resistance to cationic antimicrobial peptides, however, increased cytokine production resulting in inflammation is not seen with other palmitoylated lipid A, indicating a unique role for this modification in PA pathogenesis. © 2013 John Wiley & Sons Ltd.
ISSN: 13652958
Appears in Collections:Scopus 2011-2015

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