Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei

Abstract

Trypanosoma brucei and other African trypanosomes are vector‐borne parasites that cause substantial human suffering across sub‐Saharan Africa. The T. brucei life cycle is punctuated by numerous developmental stages, each occurring in a specific environmental niche and characterized by a unique morphology, metabolism, surface protein coat, and gene expression profile. The environmental cues and signaling pathways that drive transitions between these stages remain incompletely understood. Recent studies have started to fill this gap in knowledge. Likewise, several new studies have expanded our understanding of parasite movement through specific tissues and the parasite's ability to alter movement in response to external cues. Life cycle stage differentiation and motility are intimately integrated phenomena, as parasites must be at the right place (i.e., within a specific environmental milieu) at the right time (i.e., when they are appropriately staged and preadapted for perceiving and responding to signals) in order to complete their life cycle. In this review, we highlight some of the recent work that has transformed our understanding of signaling events that control parasite differentiation and motility. Increased knowledge of T. brucei environmental sensing and signal transduction advances our understanding of parasite biology and may direct prospective chemotherapeutic and transmission blockade strategies that are critical to eradication efforts.

A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission

“…Digenetic parasites face challenging rapid changes of biotic environments between their reservoir and vector hosts 1 . Pathways processing extracellular signals are not conserved in phylogenetically distant kinetoplastids, including Trypanosoma 2 , 3 , and the connection of identified signaling components remains to be solved. Trypanosomes shuttle between mammalian and insect hosts and are well-studied due to medical and economic impact as causative agents of neglected tropical diseases in humans and animals 4 .…”

Comment on ‘Unexpected plasticity in the life cycle of Trypanosoma brucei’

“…Notable among these are PAD family proteins that sense the change in environment upon entering the fly and stimulate parasite differentiation ( Dean et al, 2009 ). Several signalling molecules expressed by stumpy forms are also important for the initiation of parasite differentiation, as are RNA regulatory proteins ( Walsh and Hill, 2021 ). Further, as the cells initiate differentiation, they are protected from complement in the blood meal by the expression of the factor H receptor, which is enriched in stumpy forms ( Macleod et al, 2020 ).…”

A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development inTrypanosoma congolense

“…African trypanosome parasites cause substantial health and economic harms in sub– Saharan Africa through the diseases they cause in humans ( Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense ) and livestock ( Trypanosoma brucei brucei, Trypanosoma congolense, Trypanosoma vivax )[1]. T. brucei brucei in particular has been the subject of intense molecular and cellular study and there is significant understanding of their mechanisms of immune evasion by antigenic variation[2, 3], their cytological features[4, 5] and their developmental biology[6–8].…”