DETERMINING THE PHYSIOLOGICAL ROLE OF THE MECHANOSENSITIVE CHANNEL TbrMscS IN TRYPANOSOMA BRUCEI BLOODSTREAM FORMS

African sleeping sickness, also known as Human African Trypanosomiasis, is a disease primarily affecting poor sub-Saharan African communities caused by the unicellular parasite Trypanosoma brucei. T. bruceispends its lifetime split between mammalian hosts and the Tsetse fly, and both host environments present unique mechanical challenges that must be overcome for parasitic survival. Organisms adapt and respond to changing environments through a group of channels known as mechanosensitive channels, which respond to mechanical stimuli. Within T. brucei, the bacterial-like mechanosensitive channel named TbrMscS regulates the flow of ions and small osmolytes, but the extent of this channel’s impact on the physiology of the parasite is unknown. Localization studies reveal TbrMscS to be in the mitochondria of bloodstream form (BSFs) of the parasite, and qPCR analysis shows that expression in this life stage is lower than that of the procyclic forms (PCFs). Knockdown of TbrMscS in BSFs result in no difference in growth, nor was there a difference in the ability of BSFs to recover from osmotic shock. Analysis of mitochondrial membrane potential reveals that downregulation of TbrMscS results in a decrease in the mitochondrial membrane potential. Study of TbrMscS and its effects in the BSF opens avenues for insight into how the parasite survives extreme environmental changes between hosts, especially as this mechanosensitive channel presents a highly specific potential therapeutic target.