MALP-3 a Mycoplasma lipopeptide with classical endotoxic properties: end of an era of LPS monopoly?

Although some activities of LPS are shared by other bacterial components. f or half a century LPS has been regarded as unique in displaying many pathop hysiological activities. Here we report on a synthetic lipopeptide, MALP-2 from Mycoplasma fermentans, which expresses potent endotoxin-like activity and whose lethal toxicity is comparable to that of LPS. With the exception of the Limulus lysate gelation test, in which MALP-2 was approximately 1000 -fold less active than LPS, the synthetic lipopeptide induced all activitie s tested for, and in most casts to an extent comparable to that of LPS. Unl ike LPS, the biological activities of MALP-2 were expressed both in LPS-res ponder and in LPS-non-responder mice (BALB/c/l, C57BL10/ScCr), indicating t hat MALP-2 signaling, unlike that of LPS, is not transduced via the Toll-li ke receptor (Tlr) 4 protein. MALP-2 expressed no toxicity in normal or sens itized Tlr2 knockout (Tlr2(-/-)) mice indicating that its toxic activity is induced via Tlr2 signaling. The phenomenology of the lethal shock induced by MALP-2 in normal or sensitized mice, i.e. the kinetics of its developmen t and symptoms of illness exhibited by the treated animals, was very remini scent of the lethal shock induced by LPS.