Characterization of Cysteine-rich protein families of Giardia lamblia and their role during antigenic variation

MOLINA, CECILIA R.; LUJÁN, LUCAS A.; RODRÍGUEZ-WALKER, MACARENA; SAURA, ALICIA; FERNÁNDEZ, ELMER A.; LUJÁN, HUGO D.

MENDOZA

Congreso; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2022

SAIB

Giardia lamblia is an intestinal parasite known to encode several families of cysteine-rich proteins. Among these families are the "Variant-specific Surface Proteins (VSPs)", which are unquestionably involved in the process of antigenic variation. In addition to the VSPs, other families of cysteine-rich proteins have been described in Giardia, such as the “High Cysteine Membrane Proteins (HCMP)”, “High Cysteine Proteins (HCP)” and “Tenascin-like Proteins (TLP)”. However, these proteins are less well known and there is no consensus on their function, subcellular location and relationship with VSPs. Although numerous efforts have been made to determine the distinguishing features of VSPs and how many VSP genes exist in the G. lamblia genome, a clear profile of the VSP repertoire is still lacking. In this work, we perform a comprehensive analysis of Cys-rich families’ genes and proteins in the recently updated version of the Giardia genome, including their organization, characteristic features, potential evolution, and expression levels, combining pattern searches and predictions with massive sequencing techniques, integrating and reanalyzing as much omics data as possible. Our findings allow us to propose a new classification for genes and pseudogenes encoding Cys-rich proteins that better describe their involvement in Giardia biology and suggest that HCMPs play a protective role on the parasite during the turnover of one VSP by another. In addition, we design bioinformatic tools that allow comparing transcriptomes and proteomes obtained under different experimental strategies to study the biology of this and other pathogens of interest in public health.