Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal

Tettey, Mabel Deladem and Rojas, Federico and Matthews, Keith R (2022) Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal. Nature Communications, 13 (1). ISSN 2041-1723

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Abstract

Trypanosomes causing African sleeping sickness use quorum-sensing (QS) to generate transmission-competent stumpy forms in mammalian hosts. This density-dependent process is signalled by oligopeptides that stimulate the signal transduction pathway leading to stumpy formation. Here, using mass spectrometry analysis, we identify peptidases released by trypanosomes and, for 12 peptidases, confirm their extracellular delivery. Thereafter, we determine the contribution of each peptidase to QS signal production using systematic inducible overexpression in vivo, and confirm this activity operates through the physiological QS signalling pathway. Gene knockout of the QS-active peptidases identifies two enzymes, oligopeptidase B and metallocarboxypeptidase 1, that significantly reduce QS when ablated individually. Further, combinatorial gene knockout of both peptidases confirms their dominance in the generation of the QS signal, with peptidase release of oligopeptidase B mediated via an unconventional protein secretion pathway. This work identifies how the QS signal driving trypanosome virulence and transmission is generated in mammalian hosts.

Item Type:
Journal Article
Journal or Publication Title:
Nature Communications
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3100
Subjects:
ID Code:
172548
Deposited By:
Deposited On:
19 Jul 2022 08:50
Refereed?:
Yes
Published?:
Published
Last Modified:
02 Sep 2022 01:10