QIQ1-dependent bicarbonate-sensing in trypanosomes

Cells sense and adapt to their environment. Parasitic protists for example, such as African trypanosomes, occupy distinct environments in mammalian hosts, and in insect vectors, and adapt energy metabolism and growth accordingly, but the mechanisms involved remain incompletely characterized. Here we describe environmental sensing dependent upon Trypanosoma brucei Quick IQ-motif protein 1 (QIQ1). We use a genome-scale loss-of-function genetic screen to identify knockdowns associated with gain-of-fitness, or a ‘quick’ growth phenotype, in bloodstream-form cells. The dominant hit, QIQ1 (Tb927.8.6870), encodes a flagellum-localized protein with multiple putative calmodulin-binding IQ-motifs. In a competition assay, qiq1-null cells displayed a density-dependent growth advantage, which was abrogated by calcium chelation. When cells were grown at reduced density in blood serum, with a series of supplements, only bicarbonate restored the qiq1-null competitive advantage. Proteomic analysis indicated that QIQ1 increased the expression of carnitine acetyltransferase, suggesting a role in modulating fatty acid metabolism, while expression of a flagellum-localized calmodulin was both QIQ1 and bicarbonate-dependent. We conclude that trypanosomes sense and adapt to distinct environments in a QIQ1-dependent manner. Our findings suggest that QIQ1-signaling facilitates CO2-sensing to optimize utilization of available nutrients via a pathway involving calcium, calmodulin, and carnitine.