Synopsis The parasite Giardia lamblia possesses peripheral vacuoles (PVs) that function as both endosomes and lysosomes and are implicated in the adaptation, differentiation, and survival of the parasite in different environments. The mechanisms by which Giardia traffics essential proteins to these organelles and regulates their secretion have important implications in the control of parasite dissemination. In this study, we describe the participation of the heterotetrameric clathrin-adaptor protein gAP2 complex in lysosomal protein trafficking. A specific monoclonal antibody against the medium subunit (gμ2) of gAP2 showed localization of this complex to the PVs, cytoplasm, and plasma membrane in the growing trophozoites. gAP2 also colocalized with clathrin in the PVs, suggesting its involvement in endocytosis. Uptake experiments using standard molecules for the study of endocytosis revealed that gAP2 specifically participated in the endocytosis of LDL. Targeted downregulation of the gene encoding gμ2 in growing and encysting trophozoites resulted in a large decrease in the amount of cell growth and cyst wall formation, suggesting a distinct mechanism in which gAP2 is directly involved in both endocytosis and vesicular trafficking.

The protozoan parasite Giardia lamblia uses arginine deiminase (ADI) to produce energy from free L-arginine under anaerobic conditions. In this work, we demonstrate that, in addition to its known role as a metabolic enzyme, it also functions as a peptidylarginine deiminase, converting protein-bound arginine into citrulline. G. lamblia ADI specifically binds to and citrullinates the arginine in the conserved CRGKA tail of variant-specific surface proteins (VSPs), affecting both antigenic switching and antibody-mediated cell death. During encystation, ADI translocates from the cytoplasm to the nuclei and appears to play a regulatory role in the expression of encystation-specific genes. ADI is also sumoylated, which might modulate its activity. Our findings reveal a dual role played by ADI and define novel regulatory pathways used by Giardia for survival.

BackgroundIntestinal parasitoses are a major concern for public health, especially in children from middle and low-income populations of tropical and subtropical areas. We examined the presence and co-infection of parasites in humans as well as parasitic environmental contamination in Puerto Iguazú, Argentina. We explored the environmental and socio-demographic characteristics of the persistence of parasites in children and their environment.Methodology/Principal findingsThis cross-section survey was conducted among children population comprised into the area of the public health care centers of Iguazú during June 2013 to May 2016. Copro-parasitological status of 483 asymptomatic children was assessed. Simultaneously, a design-based sampling of 744 soil samples and 530 dog feces was used for characterize the environmental contamination. The 71.5% of these sites were contaminated. Sixteen genera were detected in the environment being hookworms (62.0%) the main pathogens group detected followed by Toxocara spp (16.3%), Trichuris spp (15.2%) and Giardia (6.5%). Total children prevalence raised 58.8%, detecting twelve genera of parasite with Giardia intestinalis as the most prevalent pathogen (29.0%) followed by Enterobius vermicularis (23.0%), Hymenolepis nana (12.4%) and hookworms (4.4%). Through questionnaires and census data, we characterized the socio-demographics conditions at an individual, family and neighborhood levels. A multi-level analysis including environmental contamination data showed that the ´presence of parasites´ was mostly determined by individual (e.g. age, playing habits, previous treatment) and household level (e.g. UBN, WASH, mother's literacy) determinants. Remarkably, to define the level of ‘parasite co-infection’, besides individual and household characteristics, environmental factors at a neighborhood level were important.Conclusion/SignificanceOur work represents the major survey of intestinal parasites in human and environmental samples developed in the region. High prevalence was detected in the children population as well as in their environment. This work shows the importance of considering and promoting multi-level actions over the identified determinants to face this public health problem from integrative approaches.