Sensing Host Arginine Is Essential for <i>Leishmania</i> Parasites’ Intracellular Development
Adele Goldman-Pinkovich, Sriram Kannan, Roni Nitzan-Koren, Madhu Puri, Harsh Pawar, Yael Bar-Avraham, Jacquelyn McDonald, Aakash Sur, Wen‐Wei Zhang, Greg Matlashewski, Rentala Madhubala, Shulamit Michaeli, Peter J. Myler, Dan Zilberstein
Abstract
In this study, we report that the ability of the human pathogen Leishmania to sense and monitor the lack of arginine in the phagolysosome of the host macrophage is essential for disease development. Phagolysosomes of macrophages are the niche where Leishmania resides and causes human leishmaniasis. During infection, the arginine concentration in the phagolysosome decreases as part of the host innate immune response. An arginine sensor on the Leishmania cell surface activates an arginine deprivation response pathway that upregulates the expression of a parasite arginine transporter (AAP3). Here, we use CRISPR/Cas9-mediated disruption of the AAP3 locus to show that this response enables Leishmania parasites to successfully compete with the host macrophage in the “hunger games” for arginine.