Phospholipase A1: A novel virulence factor in Trypanosoma cruzi

Abstract

Phospholipase A1 (PLA1) has been described in the infectivestages of Trypanosoma cruzi as a membrane-bound/secreted enzyme thatsignificantly modified host cell lipid profile with generation of secondlipid messengers and concomitant activation of Protein Kinase C. In thepresent work we determined higher levels of PLA1 expression in theinfective amastigotes and trypomastigotes than in the non-infectiveepimastigotes of lethal RA strain. In addition, we found similarexpression patterns but distinct PLA1 activity levels in bloodstreamtrypomastigotes from Cvd and RA (lethal) and K98 (non-lethal) T. cruzistrains, obtained at their corresponding parasitemia peaks. This fact waslikely due to the presence of different levels of anti-T. cruzi PLA1antibodies in sera of infected mice, that modulated the enzyme activity.Moreover, these antibodies significantly reduced in vitro parasiteinvasion indicating the participation of T. cruzi PLA1 in the earlyevents of parasite-host cell interaction. We also demonstrated thepresence of Lysophospholipase activity in live infective stages thatcould account for self-protection against the toxic lysophospholipidsgenerated by T. cruzi PLA1 action. At the genome level, we identified atleast eight putative genes that codify for T. cruzi PLA1 with high aminoacid sequence variability in their amino and carboxy-terminal regions; aputative PLA1 selected gene was cloned and expressed as a recombinantprotein that possessed PLA1 activity. Collectively, the results presentedhere point out at T. cruzi PLA1 as a novel virulence factor implicated inparasite invasion.