Authors contributed equally.
A divergent Pseudomonas aeruginosa palmitoyltransferase essential for cystic fibrosis-specific lipid A
Article first published online: 27 NOV 2013
© 2013 John Wiley & Sons Ltd
Volume 91, Issue 1, pages 158–174, January 2014
How to Cite
Thaipisuttikul, I., Hittle, L. E., Chandra, R., Zangari, D., Dixon, C. L., Garrett, T. A., Rasko, D. A., Dasgupta, N., Moskowitz, S. M., Malmström, L., Goodlett, D. R., Miller, S. I., Bishop, R. E. and Ernst, R. K. (2014), A divergent Pseudomonas aeruginosa palmitoyltransferase essential for cystic fibrosis-specific lipid A. Molecular Microbiology, 91: 158–174. doi: 10.1111/mmi.12451
- Issue published online: 27 DEC 2013
- Article first published online: 27 NOV 2013
- Accepted manuscript online: 6 NOV 2013 05:20AM EST
- Manuscript Accepted: 1 NOV 2013
- Canadian Institutes of Health Research. Grant Number: MOP-125979
- National Science Foundation-Major Research Instrumentation Award. Grant Number: 1029659
- National Institutes of Health. Grant Numbers: R01AI067653, RO1AI030479, R01AI047938
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.