Staphylococcus aureus deficient in lipidation of prelipoproteins is attenuated in growth and immune activation. Infect Immun 73:2411-23. ACCEPTED Downloaded from jb.asm.org at Penn State Univ on February 7 (2005)
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BibTeX
@MISC{Stoll05staphylococcusaureus,
author = {Hartmut Stoll and Jörn Dengjel and Christiane Nerz and Friedrich Götz},
title = {Staphylococcus aureus deficient in lipidation of prelipoproteins is attenuated in growth and immune activation. Infect Immun 73:2411-23. ACCEPTED Downloaded from jb.asm.org at Penn State Univ on February 7},
year = {2005}
}
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Abstract
A lipoprotein diacylglyceryl transferase (lgt) deletion mutant of Staphylococcus aureus SA113 was constructed. The lipoprotein and prelipoprotein expression, the growth behavior, and the ability of the mutant to elicit an immune response in various host cells were studied. In the wild type, the majority of [ 14 C]palmitate-labeled lipoproteins were located in the membrane fraction, although some lipoproteins were also present on the cell surface and in the culture supernatant. The lgt mutant completely lacked palmitate-labeled lipoproteins and released high amounts of some unmodified prelipoproteins, e.g., the oligopeptide-binding protein OppA, the peptidyl-prolyl cis-trans isomerase PrsA, and the staphylococcal iron transporter SitC, into the culture supernatant. The growth of the lgt mutant was hardly affected in rich medium but was retarded under nutrient limitation. The lgt mutant and its crude lysate induced much fewer proinflammatory cytokines and chemokines in human monocytic (MonoMac6), epithelial (pulmonary A549), and endothelial (human umbilical vein endothelial) cells than the wild type. However, in whole blood samples, the culture supernatant of the lgt mutant was equal or even superior to the wild-type supernatant in tumor necrosis factor alpha induction. Lipoprotein fractionation experiments provided evidence that a small proportion of the mature lipoproteins are released by the S. aureus wild type despite the lipid anchor and are trapped in part by the cell wall, thereby exposing the immune-activating lipid structure on the cell surface. Bacterial lipoproteins appear to be essential
Keyphrases
lgt mutant penn state univ infect immun staphylococcus aureus deficient culture supernatant wild type immune activation cell surface palmitate-labeled lipoprotein pulmonary a549 wild-type supernatant lipid anchor growth behavior immune response various host cell membrane fraction oligopeptide-binding protein oppa bacterial lipoprotein nutrient limitation lipoprotein diacylglyceryl transferase deletion mutant mature lipoprotein rich medium small proportion crude lysate unmodified prelipoproteins immune-activating lipid structure human umbilical vein endothelial staphylococcal iron transporter sitc cell wall whole blood sample proinflammatory cytokine lipoprotein fractionation experiment high amount prelipoprotein expression peptidyl-prolyl cis-trans isomerase prsa tumor necrosis factor alpha induction
