Toxoplasma membrane inositol phospholipid binding protein TgREMIND is essential for secretory organelle function and host infection.

Apicomplexan parasites possess specialized secretory organelles called rhoptries, micronemes, and dense granules that play a vital role in host infection. In this study, we demonstrate that TgREMIND, a protein found in Toxoplasma gondii, is necessary for the biogenesis of rhoptries and dense granules. TgREMIND contains a Fes-CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain, which binds to membrane phospholipids, as well as a novel uncharacterized domain that we have named REMIND (regulator of membrane-interacting domain). Both the F-BAR domain and the REMIND are crucial for TgREMIND functions. When TgREMIND is depleted, there is a significant decrease in the abundance of dense granules and abnormal transparency of rhoptries, leading to a reduction in protein secretion from these organelles. The absence of TgREMIND inhibits host invasion and parasite dissemination, demonstrating that TgREMIND is essential for the proper function of critical secretory organelles required for successful infection by Toxoplasma.

An image-based high-content screening for compounds targeting Toxoplasma gondii repurposed inhibitors effective against the malaria parasite Plasmodium falciparum.

Apicomplexa phylum includes numerous obligate intracellular protozoan parasites that are life threatening for humans and animals. In this context, Plasmodium falciparum and Toxoplasma gondii are of particular interest, as they are responsible for malaria and toxoplasmosis, respectively, for which efficient vaccines are presently lacking and therapies need to be improved. Apicomplexan parasites have a highly polarized morphology, with their apical end containing specific secretory organelles named rhoptries and micronemes, which depend on the unique receptor and transporter sortilin TgSORT for their biogenesis. In the present study, we took advantage of the subcellular polarity of the parasite to engineer a clonal transgenic Toxoplasma line that expresses simultaneously the green fluorescent protein TgSORT-GFP in the post-Golgi-endosome-like compartment and the red fluorescent protein rhoptry ROP1-mCherry near the apical end. We utilized this fluorescent transgenic T. gondii to develop a miniaturized image-based phenotype assay coupled to an automated image analysis. By applying this methodology to 1,120 compounds, we identified 12 that are capable of disrupting the T. gondii morphology and inhibiting intracellular replication. Analysis of the selected compounds confirmed that all 12 are kinase inhibitors and intramembrane pumps, with some exhibiting potent activity against Plasmodium falciparum. Our findings highlight the advantage of comparative and targeted phenotypic analysis involving two related parasite species as a means of identifying molecules with a conserved mode of action.

Comparison of motorcycle taxi driver's respiratory health using an air quality standard for carbon monoxide in ambient air: a pilot survey in Benin.

INTRODUCTION: Ambient air quality standards are not designed to protect people occupationally exposed to outdoor air pollution on a routine basis. This study aimed to assess the effect of exceeding the US ambient air quality standard for carbon monoxide (CO) on motorcycle taxi drivers respiratory health. METHODS: A cross-sectional study of 85 current motorcycle taxi drivers with at least 5 years of job tenure in Cotonou (Benin) was conducted. Personal CO was measured with a portable CO data logger for 8 hours per day during working hours. A questionnaire on respiratory symptoms was administered to participants and spirometry was performed. Participants were divided into two groups, those with exposure to CO >9 ppm and ≤9 ppm, according to the US Environmental Protection Agency (EPA) National Ambient Air Quality Standard which is an 8-hour average of 9ppm. 8 and 10 ppm were also used an exposure limit. Analysis was done using these two groups. RESULTS: Socio-demographic characteristics were well balanced between the two study groups. The drivers with a CO exposure of more than 9ppm had non-significantly more respiratory symptoms (OR=1.67; 95%CI:0.26,10.74), lower FVC and FEV1 compared to the less exposed group but they have a significant lower PEF (-10%, p=0.02). When we used an exposure limit of 8 or 10 ppm the results were not statistically different. CONCLUSION: Drivers with a CO exposure >9 ppm tend to have more respiratory problems. More research is needed to reinforce this result in order to improve air quality standards to protect workers occupationally exposed to outdoor air pollution.