Differential Distribution of Genes Encoding the Virulence Factor <em>Trans</em>-Sialidase along <em>Trypanosoma cruzi</em> Discrete Typing Units

<div><p><i>Trypanosoma cruzi</i> the agent of Chagas disease is a monophyletic but heterogeneous group conformed by several Discrete Typing Units (DTUs) named TcI to TcVI characterized by genetic markers. The <i>trans</i>-sialidase (TS) is a virulence factor involved in cell invasion and pathogenesis that is differentially expressed in aggressive and less virulent parasite stocks. Genes encoding TS-related proteins are included in a large family divided in several groups but only one of them contains <i>TS</i> genes. Two closely related genes differing in a T/C transition encode the enzymatically active TS (aTS) and a lectin-like TS (iTS). We quantified the <i>aTS/iTS</i> genes from TcII and TcVI aggressive and TcI low virulent strains and found variable <i>aTS</i> number (1–32) per haploid genome. In spite of being low TS enzyme-expressers, TcI strains carry 28–32 <i>aTS</i> gene copies. The intriguing absence of <i>iTS</i> genes in TcI strains together with the presence of aTS/iTS in TcII and TcVI strains (virulent) were observed. Moreover, after sequencing <i>aTS/iTS</i> from 38 isolates collected along the Americas encompassing all DTUs, the persistent absence of the <i>iTS</i> gene in TcI, TcIII and TcIV was found. In addition, the sequence clustering together with T/C transition analysis correlated to DTUs of <i>T. cruzi</i>. The consistence of <i>TS</i> results with both evolutionary genome models proposed for <i>T. cruzi</i>, namely the “Two Hybridization” and the “Three Ancestor” was discussed and reviewed to fit present findings. Parasite stocks to attempt genetic KO or to assay the involvement of iTS in parasite biology and virulence are finally available.</p>