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Infection and Immunity, October 1998, p. 4804-4810, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Structure and Specific Activity of Macrophage-Stimulating Lipopeptides from Mycoplasma hyorhinis

Peter F. Mühlradt,1,* Michael Kiess,1 Holger Meyer,1,dagger Roderich Süssmuth,2 and Günther Jung2

Immunobiology and Structure Research Groups, Gesellschaft für Biotechnologische Forschung mbH, D-38124 Braunschweig,1 and Institut für Organische Chemie der Universität Tübingen, D-72076 Tübingen,2 Germany

Received 8 April 1998/Returned for modification 25 May 1998/Accepted 23 July 1998

Mycoplasmas are potent macrophage stimulators. We describe the isolation of macrophage-stimulatory lipopeptides S-[2,3-bisacyl(C16:0/C18:0)oxypropyl]cysteinyl-GQTDNNSSQSQQPGSGTTNT and S-[2,3-bisacyl(C16:0/C18:0)oxypropyl]cysteinyl-GQTN derived from the Mycoplasma hyorhinis variable lipoproteins VlpA and VlpC, respectively. These lipopeptides were characterized by amino acid sequence and composition analysis and by mass spectrometry. The lipopeptides S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-GQTNT and S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-SKKKK and the N-palmitoylated derivative of the latter were synthesized, and their macrophage-stimulatory activities were compared in a nitric oxide release assay with peritoneal macrophages from C3H/HeJ mice. The lipopeptides with the free amino terminus showed half-maximal activity at 3 pM regardless of their amino acid sequence; i.e., they were as active as the previously isolated M. fermentans-derived lipopeptide MALP-2. The macrophage-stimulatory activity of the additionally N-palmitoylated lipopeptide or of the murein lipoprotein from Escherichia coli, however, was lower by orders of magnitude. It is concluded that the lack of N-acyl groups in mycoplasmal lipoproteins explains their exceptionally high in vitro macrophage-stimulatory capacity. Certain features that lipopolysaccharide endotoxin and mycoplasmal lipopeptides have in common are discussed. Lipoproteins and lipopeptides are likely to be the main causative agents of inflammatory reactions to mycoplasmas. This may be relevant in the context of mycoplasmas as arthritogenic pathogens and their association with AIDS.

* Corresponding author. Mailing address: Immunobiology Research Group, Gesellschaft für Biotechnologische Forschung m.b.H., Mascheroderweg 1, D-38124 Braunschweig, Germany. Phone: 49-531-6181-240. Fax: 49-531-6181-284. E-mail: PFM{at}GBF.DE.

dagger Present address: Biesterfeld Plastic GmbH, D-20095 Hamburg, Germany.

Infection and Immunity, October 1998, p. 4804-4810, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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