Institute of Cell Biology, University of Bern, Bern, Switzerland.
Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Nat Commun. 2022 Feb 1;13(1):603. doi: 10.1038/s41467-022-28293-w.
The collective movement of African trypanosomes on semi-solid surfaces, known as social motility, is presumed to be due to migration factors and repellents released by the parasites. Here we show that procyclic (insect midgut) forms acidify their environment as a consequence of glucose metabolism, generating pH gradients by diffusion. Early and late procyclic forms exhibit self-organising properties on agarose plates. While early procyclic forms are repelled by acid and migrate outwards, late procyclic forms remain at the inoculation site. Furthermore, trypanosomes respond to exogenously formed pH gradients, with both early and late procyclic forms being attracted to alkali. pH taxis is mediated by multiple cyclic AMP effectors: deletion of one copy of adenylate cyclase ACP5, or both copies of the cyclic AMP response protein CARP3, abrogates the response to acid, while deletion of phosphodiesterase PDEB1 completely abolishes pH taxis. The ability to sense pH is biologically relevant as trypanosomes experience large changes as they migrate through their tsetse host. Supporting this, a CARP3 null mutant is severely compromised in its ability to establish infections in flies. Based on these findings, we propose that the expanded family of adenylate cyclases in trypanosomes might govern other chemotactic responses in their two hosts.
非洲锥体虫在半固态表面上的集体运动，称为社会运动性，据推测是由于寄生虫释放的迁移因子和驱避剂所致。在这里，我们表明，前鞭毛体（昆虫中肠）形式由于葡萄糖代谢而酸化其环境，通过扩散产生 pH 梯度。早期和晚期前鞭毛体在琼脂糖平板上表现出自组织特性。虽然早期前鞭毛体被酸排斥并向外迁移，但晚期前鞭毛体仍留在接种部位。此外，锥体虫对体外形成的 pH 梯度作出反应，早期和晚期前鞭毛体均被碱吸引。pH 趋化性由多种环腺苷酸效应物介导：删除一个腺苷酸环化酶 ACP5 或两个环腺苷酸反应蛋白 CARP3 的拷贝，都会破坏对酸的反应，而磷酸二酯酶 PDEB1 的缺失则完全消除 pH 趋化性。感知 pH 的能力在生物学上是相关的，因为当锥体虫在其采采蝇宿主中迁移时，它们会经历巨大的变化。支持这一观点的是，CARP3 缺失突变体在其在蝇类中建立感染的能力严重受损。基于这些发现，我们提出，锥体虫中扩增的腺苷酸环化酶家族可能控制其两个宿主中的其他趋化反应。
