Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.

Vibrio species, which include several pathogens, are autochthonous to estuarine and warm coastal marine environments, where biofilm formation bolsters their ecological persistence and transmission. Here, we identify a bicistronic operon, rcbAB, whose products synergistically inhibit motility and pro...

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Main Authors: Shobnom Mustaree, Ram Podicheti, Doug Rusch, Dean A Rowe-Magnus
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1013353
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author Shobnom Mustaree
Ram Podicheti
Doug Rusch
Dean A Rowe-Magnus
author_facet Shobnom Mustaree
Ram Podicheti
Doug Rusch
Dean A Rowe-Magnus
author_sort Shobnom Mustaree
collection DOAJ
description Vibrio species, which include several pathogens, are autochthonous to estuarine and warm coastal marine environments, where biofilm formation bolsters their ecological persistence and transmission. Here, we identify a bicistronic operon, rcbAB, whose products synergistically inhibit motility and promote biofilm maturation post-attachment by modulating intracellular c-di-GMP levels in the human and animal pathogen V. vulnificus. RcbA contains an N-terminal tetratricopeptide repeat (TPR) domain and a structured C-terminal region of unknown function, while RcbB possesses an N-terminal TPR domain and a C-terminal GGDEF domain characteristic of diguanylate cyclases. The TPR domain of RcbB represses its diguanylate cyclase activity, while RcbA's TPR domain and C-terminal region co-operatively de-repress it. Localization of both proteins to the flagellar pole is TPR-dependent but not co-dependent, although RcbA anchors RcbB to the pole in the absence of polar landmarks such as HubP and flagella. The conservation of rcbAB across diverse bacterial taxa substantiates its fundamental importance in bacterial biology. This work demonstrates how spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling, contributing to our understanding of biofilm formation in Vibrio species and potentially other bacteria. It also reveals the first evidence of inter-protein interaction via the TPR domains of both partners, challenging the conventional paradigm in which only one bears the domain.
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spelling doaj-art-6af9ef2f4aa54c1fbdf7ffc12b4060852025-08-20T03:13:39ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-07-01217e101335310.1371/journal.ppat.1013353Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.Shobnom MustareeRam PodichetiDoug RuschDean A Rowe-MagnusVibrio species, which include several pathogens, are autochthonous to estuarine and warm coastal marine environments, where biofilm formation bolsters their ecological persistence and transmission. Here, we identify a bicistronic operon, rcbAB, whose products synergistically inhibit motility and promote biofilm maturation post-attachment by modulating intracellular c-di-GMP levels in the human and animal pathogen V. vulnificus. RcbA contains an N-terminal tetratricopeptide repeat (TPR) domain and a structured C-terminal region of unknown function, while RcbB possesses an N-terminal TPR domain and a C-terminal GGDEF domain characteristic of diguanylate cyclases. The TPR domain of RcbB represses its diguanylate cyclase activity, while RcbA's TPR domain and C-terminal region co-operatively de-repress it. Localization of both proteins to the flagellar pole is TPR-dependent but not co-dependent, although RcbA anchors RcbB to the pole in the absence of polar landmarks such as HubP and flagella. The conservation of rcbAB across diverse bacterial taxa substantiates its fundamental importance in bacterial biology. This work demonstrates how spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling, contributing to our understanding of biofilm formation in Vibrio species and potentially other bacteria. It also reveals the first evidence of inter-protein interaction via the TPR domains of both partners, challenging the conventional paradigm in which only one bears the domain.https://doi.org/10.1371/journal.ppat.1013353
spellingShingle Shobnom Mustaree
Ram Podicheti
Doug Rusch
Dean A Rowe-Magnus
Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.
PLoS Pathogens
title Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.
title_full Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.
title_fullStr Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.
title_full_unstemmed Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.
title_short Spatio-genetically coordinated TPR domain-containing proteins modulate c-di-GMP signaling in Vibrio vulnificus.
title_sort spatio genetically coordinated tpr domain containing proteins modulate c di gmp signaling in vibrio vulnificus
url https://doi.org/10.1371/journal.ppat.1013353
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AT dougrusch spatiogeneticallycoordinatedtprdomaincontainingproteinsmodulatecdigmpsignalinginvibriovulnificus
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