Cyclic AMP Regulates Social Behavior in African Trypanosomes

ABSTRACT The protozoan parasite Trypanosoma brucei engages in surface-induced social behavior, termed social motility, characterized by single cells assembling into multicellular groups that coordinate their movements in response to extracellular signals. Social motility requires sensing and respond...

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Autores principales:	Michael Oberholzer, Edwin A. Saada, Kent L. Hill
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d31b097be0cc4a45996fe936ab44f0b8
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spelling	oai:doaj.org-article:d31b097be0cc4a45996fe936ab44f0b82021-11-15T15:49:02ZCyclic AMP Regulates Social Behavior in African Trypanosomes10.1128/mBio.01954-142150-7511https://doaj.org/article/d31b097be0cc4a45996fe936ab44f0b82015-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01954-14https://doaj.org/toc/2150-7511ABSTRACT The protozoan parasite Trypanosoma brucei engages in surface-induced social behavior, termed social motility, characterized by single cells assembling into multicellular groups that coordinate their movements in response to extracellular signals. Social motility requires sensing and responding to extracellular signals, but the underlying mechanisms are unknown. Here we report that T. brucei social motility depends on cyclic AMP (cAMP) signaling systems in the parasite's flagellum (synonymous with cilium). Pharmacological inhibition of cAMP-specific phosphodiesterase (PDE) completely blocks social motility without impacting the viability or motility of individual cells. Using a fluorescence resonance energy transfer (FRET)-based sensor to monitor cAMP dynamics in live cells, we demonstrate that this block in social motility correlates with an increase in intracellular cAMP levels. RNA interference (RNAi) knockdown of the flagellar PDEB1 phenocopies pharmacological PDE inhibition, demonstrating that PDEB1 is required for social motility. Using parasites expressing distinct fluorescent proteins to monitor individuals in a genetically heterogeneous community, we found that the social motility defect of PDEB1 knockdowns is complemented by wild-type parasites in trans. Therefore, PDEB1 knockdown cells are competent for social motility but appear to lack a necessary factor that can be provided by wild-type cells. The combined data demonstrate that the role of cyclic nucleotides in regulating microbial social behavior extends to African trypanosomes and provide an example of transcomplementation in parasitic protozoa. IMPORTANCE In bacteria, studies of cell-cell communication and social behavior have profoundly influenced our understanding of microbial physiology, signaling, and pathogenesis. In contrast, mechanisms underlying social behavior in protozoan parasites are mostly unknown. Here we show that social behavior in the protozoan parasite Trypanosoma brucei is governed by cyclic-AMP signaling systems in the flagellum, with intriguing parallels to signaling systems that control bacterial social behavior. We also generated a T. brucei social behavior mutant and found that the mutant phenotype is complemented by wild-type cells grown in the same culture. Our findings open new avenues for dissecting social behavior and signaling in protozoan parasites and illustrate the capacity of these organisms to influence each other's behavior in mixed communities.Michael OberholzerEdwin A. SaadaKent L. HillAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 3 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Michael Oberholzer Edwin A. Saada Kent L. Hill Cyclic AMP Regulates Social Behavior in African Trypanosomes
description	ABSTRACT The protozoan parasite Trypanosoma brucei engages in surface-induced social behavior, termed social motility, characterized by single cells assembling into multicellular groups that coordinate their movements in response to extracellular signals. Social motility requires sensing and responding to extracellular signals, but the underlying mechanisms are unknown. Here we report that T. brucei social motility depends on cyclic AMP (cAMP) signaling systems in the parasite's flagellum (synonymous with cilium). Pharmacological inhibition of cAMP-specific phosphodiesterase (PDE) completely blocks social motility without impacting the viability or motility of individual cells. Using a fluorescence resonance energy transfer (FRET)-based sensor to monitor cAMP dynamics in live cells, we demonstrate that this block in social motility correlates with an increase in intracellular cAMP levels. RNA interference (RNAi) knockdown of the flagellar PDEB1 phenocopies pharmacological PDE inhibition, demonstrating that PDEB1 is required for social motility. Using parasites expressing distinct fluorescent proteins to monitor individuals in a genetically heterogeneous community, we found that the social motility defect of PDEB1 knockdowns is complemented by wild-type parasites in trans. Therefore, PDEB1 knockdown cells are competent for social motility but appear to lack a necessary factor that can be provided by wild-type cells. The combined data demonstrate that the role of cyclic nucleotides in regulating microbial social behavior extends to African trypanosomes and provide an example of transcomplementation in parasitic protozoa. IMPORTANCE In bacteria, studies of cell-cell communication and social behavior have profoundly influenced our understanding of microbial physiology, signaling, and pathogenesis. In contrast, mechanisms underlying social behavior in protozoan parasites are mostly unknown. Here we show that social behavior in the protozoan parasite Trypanosoma brucei is governed by cyclic-AMP signaling systems in the flagellum, with intriguing parallels to signaling systems that control bacterial social behavior. We also generated a T. brucei social behavior mutant and found that the mutant phenotype is complemented by wild-type cells grown in the same culture. Our findings open new avenues for dissecting social behavior and signaling in protozoan parasites and illustrate the capacity of these organisms to influence each other's behavior in mixed communities.
format	article
author	Michael Oberholzer Edwin A. Saada Kent L. Hill
author_facet	Michael Oberholzer Edwin A. Saada Kent L. Hill
author_sort	Michael Oberholzer
title	Cyclic AMP Regulates Social Behavior in African Trypanosomes
title_short	Cyclic AMP Regulates Social Behavior in African Trypanosomes
title_full	Cyclic AMP Regulates Social Behavior in African Trypanosomes
title_fullStr	Cyclic AMP Regulates Social Behavior in African Trypanosomes
title_full_unstemmed	Cyclic AMP Regulates Social Behavior in African Trypanosomes
title_sort	cyclic amp regulates social behavior in african trypanosomes
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/d31b097be0cc4a45996fe936ab44f0b8
work_keys_str_mv	AT michaeloberholzer cyclicampregulatessocialbehaviorinafricantrypanosomes AT edwinasaada cyclicampregulatessocialbehaviorinafricantrypanosomes AT kentlhill cyclicampregulatessocialbehaviorinafricantrypanosomes
_version_	1718427488687751168

Cyclic AMP Regulates Social Behavior in African Trypanosomes

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