VARIANT-SPECIFIC SURFACE PROTEINS AS MEDIATORS OF ANTIGENIC VARIATION IN Giardia lamblia

ALBANO HERALDO TENAGLIA; HUGO DANIEL LUJÁN; DIEGO NICOLÁS RÍOS; PABLO RUBÉN GARGANTINI; ALESSANDRO TORRI

Córdoba

Congreso; 52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology (SAIB); 2016

SAIB

Giardia lamblia colonizes the upper small intestine of humans and other vertebrates causing giardiasis. Like many pathogenicmicroorganisms, Giardia undergoes antigenic variation (AV), a process that contributes to the production of chronic and/or recurrentinfections. The surface of Giardia trophozoites is covered by a dense coat of Variant-specific Surface Proteins (VSPs), whichrepresents the interface between the parasite and the environment. Giardia possesses ~200 VSP genes, but only one VSP is expressedon its surface at a particular time. The stimulus that triggers VSP switching is unknown. VSP are integral membrane proteinscomprising a variable extracellular domain and a highly conserved C-terminal region including transmembrane domain and a shortcytoplasmic tail. In this work, we show that anti-VSP immunoglobulins (Igs) are not cytotoxic to Giardia, as previously reported, butthey increase the rate of VSP switching. Besides, we prove that anti-VSP Igs increase the Giardia reduced state, which could be linkedto the initiation of a still unclear intracellular signal triggered by the presence of the anti-VSP Igs. By using fragmented anti-VSP Igsand point mutations in the conserved C-terminal domain of VSPs, we demonstrate that AV in Giardia is a complex mechanisminvolving both external and cellular processes linked by the particular structure of the VSPs.