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

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal. / Tettey, Mabel Deladem; Rojas, Federico; Matthews, Keith R.
In: Nature Communications, Vol. 13, No. 1, 3322, 09.06.2022.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Tettey, MD, Rojas, F & Matthews, KR 2022, 'Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal', Nature Communications, vol. 13, no. 1, 3322. https://doi.org/10.1038/s41467-022-31057-1

APA

Tettey, M. D., Rojas, F., & Matthews, K. R. (2022). Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal. Nature Communications, 13(1), Article 3322. https://doi.org/10.1038/s41467-022-31057-1

Vancouver

Tettey MD, Rojas F, Matthews KR. Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal. Nature Communications. 2022 Jun 9;13(1):3322. doi: 10.1038/s41467-022-31057-1

Author

Tettey, Mabel Deladem ; Rojas, Federico ; Matthews, Keith R. / Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{a721c4ffc38542dcb6e3b8ac41e3b083,
title = "Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal",
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.",
keywords = "Animals, Mammals, Peptide Hydrolases/genetics, Quorum Sensing/genetics, Trypanosoma, Trypanosoma brucei brucei/metabolism, Trypanosomiasis, African",
author = "Tettey, {Mabel Deladem} and Federico Rojas and Matthews, {Keith R}",
year = "2022",
month = jun,
day = "9",
doi = "10.1038/s41467-022-31057-1",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal

AU - Tettey, Mabel Deladem

AU - Rojas, Federico

AU - Matthews, Keith R

PY - 2022/6/9

Y1 - 2022/6/9

N2 - 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.

AB - 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.

KW - Animals

KW - Mammals

KW - Peptide Hydrolases/genetics

KW - Quorum Sensing/genetics

KW - Trypanosoma

KW - Trypanosoma brucei brucei/metabolism

KW - Trypanosomiasis, African

U2 - 10.1038/s41467-022-31057-1

DO - 10.1038/s41467-022-31057-1

M3 - Journal article

C2 - 35680928

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3322

ER -