Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides

Abigail Clements, Dedreia Tull, Adam W Jenney, Jacinta L Farn, Sang-Hyun Kim, Russell E Bishop, Joseph B McPhee, Robert EW Hancock, Elizabeth Louise Hartland, Martin J Pearse, Odilia LC Wijburg, David C Jackson, Malcolm J McConville, Richard Anthony Strugnell

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Abstract

Klebsiella pneumoniae is an important cause of nosocomial Gram-negative sepsis. Lipopolysaccharide (LPS) is considered to be a major virulence determinant of this encapsulated bacterium and most mutations to the lipid A anchor of LPS are conditionally lethal to the bacterium. We studied the role of LPS acylation in K. pneumoniae disease pathogenesis by using a mutation of lpxM (msbB/waaN), which encodes the enzyme responsible for late secondary acylation of immature lipid A molecules. A K. pneumoniae B5055 (K2:O1) lpxM mutant was found to be attenuated for growth in the lungs in a mouse pneumonia model leading to reduced lethality of the bacterium. B5055lpxM exhibited similar sensitivity to phagocytosis or complement-mediated lysis than B5055, unlike the non-encapsulated mutant B5055nm. In vitro, B5055lpxM showed increased permeability of the outer membrane and an increased susceptibility to certain antibacterial peptides suggesting that in vivo attenuation may be due in part to sensitivity to antibacterial peptides present in the lungs of BALB/c mice. These data support the view that lipopolysaccharide acylation plays a important role in providing Gram negative bacteria some resistance to structural and innate defences and especially the antibacterial properties of detergents (eg. bile) and cationic defensins.
Original languageEnglish
Pages (from-to)15569 - 15577
Number of pages9
JournalThe Journal of Biological Chemistry
Volume282
Issue number21
Publication statusPublished - 2007

Cite this

Clements, A., Tull, D., Jenney, A. W., Farn, J. L., Kim, S-H., Bishop, R. E., McPhee, J. B., Hancock, R. EW., Hartland, E. L., Pearse, M. J., Wijburg, O. LC., Jackson, D. C., McConville, M. J., & Strugnell, R. A. (2007). Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides. The Journal of Biological Chemistry, 282(21), 15569 - 15577.