Trypanosoma cruzi long chain solanesyl pyrophosphate synthase (TcSPPS): interstrain variability, polymeric structure and recognition by chagasic sera

BONTEMPI, EJ; DEBENJAK, JA; PRAVIA, CA; FUSCO, O; PERRONE, A; GARAVAGLIA, PA; GARCIA, GA; CANNATA, JB; FICHERA, LE; BUA, J; MAIDANA, C; LAURICELLA, M; ANDERSOON, B; RODRIGUEZ, JB

Santa Fe, Prov. Sta. Fe, Argentina

Congreso; XXIII Reunión Científica Anual de la Sociedad Argentina de Protozoología; 2009

Sociedad Argentina de Protozoologia

We already published the characterization of the TcSPPS [Ferella 2006] and the degree of inhibition of the enzyme by new 2-alkylaminoethyl-1,1-bisphosphonic acids [Szajnman 2008]. Although most of them were more specific for T. cruzi Farnesyl Diphosphate Synthase, compound 19 was four times more effective against TcSPPS (50% inhibition at 252 nanoM). Additionally, at a 4.1 microM concentration the inhibitor slowed down amastigotes growth. An interstrain study of the variability of TcSPPS disclosed a new version of the gene, differing in nine nucleotides that result in 3 amino acid changes. Based on the typification of the strains, it seems that an ancestor in lineage IIb carried the old version, that was later transmitted to group IIe. The differences between the enzyme versions do not seem to affect greatly the interaction with compound 19, as demonstrated measuring the concentration of the compound diminishing by 50% the growth of parasites carrying any of the two versions. The polymeric structure of TcSPPS, studied by cross-linking and gel filtration experiments, showed  that the native protein adopts mainly a dimeric conformation, with a subpopulation adopting tetrameric conformation. Thirty chronic chagasic patients sera were unable to recognize TcSPPS by ELISA, suggesting the protein is present in low amounts or is not very immunogenic in humans.