{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:07:41Z","timestamp":1790233661590,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Lipoproteins (Lpp) are ligands of TLR2 and signal by the adaptor MyD88. As part of the bacterial cell envelope, Lpp are mainly involved in nutrient acquisition for Staphylococcus aureus. The impact of Lpp on TLR2-MyD88 activation for S. aureus in systemic infection is unknown. S. aureus strain SA113 deficient in the enzyme encoded by the prolipoprotein diacylglyceryl transferase gene (\u0394lgt), which attaches the lipid anchor to pro-Lpp, was used to study benefits and costs of Lpp maturation. Lpp in S. aureus induced early and strong cytokines by TLR2-MyD88 signaling in murine peritoneal macrophages. Lpp contributed via TLR2 to pathogenesis of sepsis in C57BL\/6 mice with IL-1\u03b2, chemokine-mediated inflammation, and high bacterial numbers. In the absence of MyD88-mediated inflammation, Lpp allowed bacterial clearing from liver devoid of infiltrating cells, but still conferred a strong growth advantage in mice, which was shown to rely on iron uptake and storage in vitro and in vivo. With iron-restricted bacteria, the Lpp-related growth advantage was evident in infection of MyD88\u2212\/\u2212, but not of C57BL\/6, mice. On the other hand, iron overload of the host restored the growth deficit of \u0394lgt in MyD88\u2212\/\u2212, but not in immunocompetent C57BL\/6 mice. These results indicate that iron acquisition is improved by Lpp of S. aureus but is counteracted by inflammation. Thus, lipid anchoring is an evolutionary advantage for S. aureus to retain essential proteins for better survival in infection.<\/jats:p>","DOI":"10.4049\/jimmunol.0804292","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T21:00:29Z","timestamp":1242766829000},"page":"7110-7118","source":"Crossref","is-referenced-by-count":79,"title":["Lipoproteins in <i>Staphylococcus aureus<\/i> Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo"],"prefix":"10.1093","volume":"182","author":[{"given":"Mathias","family":"Schmaler","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Division Infection Biology, University Hospital Basel , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naja J","family":"Jann","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division Infection Biology, University Hospital Basel , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Ferracin","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division Infection Biology, University Hospital Basel , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea Z","family":"Landolt","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division Infection Biology, University Hospital Basel , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalitha","family":"Biswas","sequence":"additional","affiliation":[{"name":"Microbial Genetics, University T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"G\u00f6tz","sequence":"additional","affiliation":[{"name":"Microbial Genetics, University T\u00fcbingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine","family":"Landmann","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division Infection Biology, University Hospital Basel , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,6,1]]},"reference":[{"key":"2025032715455797400_R1","first-page":"2411","article-title":"Staphylococcus aureus deficient in lipidation of prelipoproteins is attenuated in growth and immune activation.","volume-title":"Infect. 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Immun.","year":"2000"},{"key":"2025032715455797400_R6","first-page":"28815","article-title":"Heme coordination by Staphylococcus aureus IsdE.","volume-title":"J. Biol. Chem.","year":"2007"},{"key":"2025032715455797400_R7","first-page":"1626","article-title":"Iron-source preference of Staphylococcus aureus infections.","volume-title":"Science","year":"2004"},{"key":"2025032715455797400_R8","first-page":"6820","article-title":"Structure-function relationship of bacterial prolipoprotein diacylglyceryl transferase: functionally significant conserved regions.","volume-title":"J. Bacteriol.","year":"1995"},{"key":"2025032715455797400_R9","first-page":"9147","article-title":"Characterization of N-terminal structure of TLR2-activating lipoprotein in Staphylococcus aureus.","volume-title":"J. Biol. Chem.","year":"2009"},{"key":"2025032715455797400_R10","first-page":"8406","article-title":"The triacylated ATP binding cluster transporter substrate-binding lipoprotein of Staphylococcus aureus functions as a native ligand for the Toll-like receptor 2.","volume-title":"J. Biol. Chem.","year":"2009"},{"key":"2025032715455797400_R11","first-page":"736","article-title":"Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2.","volume-title":"Science","year":"1999"},{"key":"2025032715455797400_R12","first-page":"459","article-title":"Recognition of lipopeptides by Toll-like receptors.","volume-title":"J Endotoxin Res.","year":"2002"},{"key":"2025032715455797400_R13","first-page":"355","article-title":"Lipoprotein is a predominant Toll-like receptor 2 ligand in Staphylococcus aureus cell wall components.","volume-title":"Int. Immunol.","year":"2006"},{"key":"2025032715455797400_R14","first-page":"732","article-title":"Host defense mechanisms triggered by microbial lipoproteins through Toll-like receptors.","volume-title":"Science","year":"1999"},{"key":"2025032715455797400_R15","first-page":"2382","article-title":"Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by Toll-like receptor 2.","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032715455797400_R16","first-page":"33419","article-title":"Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.","volume-title":"J. Biol. Chem.","year":"1999"},{"key":"2025032715455797400_R17","first-page":"525","article-title":"Activation and regulation of Toll-like receptors 2 and 1 in human leprosy.","volume-title":"Nat. Med.","year":"2003"},{"key":"2025032715455797400_R18","first-page":"3162","article-title":"Not lipoteichoic acid but lipoproteins appear to be the dominant immunobiologically active compounds in Staphylococcus aureus.","volume-title":"J. Immunol.","year":"2006"},{"key":"2025032715455797400_R19","first-page":"1071","article-title":"Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.","volume-title":"Cell","year":"2007"},{"key":"2025032715455797400_R20","first-page":"17406","article-title":"Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2.","volume-title":"J. Biol. 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Microbiol.","year":"2001"},{"key":"2025032715455797400_R35","first-page":"885","article-title":"The immunopathogenesis of sepsis.","volume-title":"Nature","year":"2002"},{"key":"2025032715455797400_R36","first-page":"755","article-title":"Mapping the pathways to staphylococcal pathogenesis by comparative secretomics.","volume-title":"Microbiol. Mol. Biol. Rev.","year":"2006"},{"key":"2025032715455797400_R37","first-page":"69","article-title":"Iron homeostasis.","volume-title":"Annu. Rev. Physiol.","year":"2007"},{"key":"2025032715455797400_R38","first-page":"351","article-title":"Influences of \u03c2B and agr on expression of staphylococcal enterotoxin B (seb) in Staphylococcus aureus.","volume-title":"Can. J. Microbiol.","year":"2004"},{"key":"2025032715455797400_R39","first-page":"6933","article-title":"Inflammasome-mediated production of IL-1\u03b2 is required for neutrophil recruitment against Staphylococcus aureus in vivo.","volume-title":"J. 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