Staphylococcus aureusDeficient in Lipidation of Prelipoproteins Is Attenuated in Growth and Immune Activation
| Autor: | Jörn Dengjel, Hartmut Stoll, Christiane Nerz, Friedrich Götz |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Staphylococcus aureus
Chemokine Lipoproteins Immunology Mutant Protein Sorting Signals Biology medicine.disease_cause Microbiology Monocytes Proinflammatory cytokine Immune system Transferases Operon medicine Humans Tumor Necrosis Factor-alpha Wild type Molecular Pathogenesis Infectious Diseases biology.protein Parasitology Tumor necrosis factor alpha Genome Bacterial Interleukin-1 Lipoprotein |
| Zdroj: | Infection and Immunity. 73:2411-2423 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | A lipoprotein diacylglyceryl transferase (lgt) deletion mutant ofStaphylococcus aureusSA113 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 [14C]palmitate-labeled lipoproteins were located in the membrane fraction, although some lipoproteins were also present on the cell surface and in the culture supernatant. Thelgtmutant completely lacked palmitate-labeled lipoproteins and released high amounts of some unmodified prelipoproteins, e.g., the oligopeptide-binding protein OppA, the peptidyl-prolylcis-transisomerase PrsA, and the staphylococcal iron transporter SitC, into the culture supernatant. The growth of thelgtmutant was hardly affected in rich medium but was retarded under nutrient limitation. Thelgtmutant 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 thelgtmutant 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 theS. aureuswild 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 for a complete immune stimulation by gram-positive bacteria. |
| Databáze: | OpenAIRE |
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