The Prc and CtpA proteases modulate cell-surface signaling activity and virulence in Pseudomonas aeruginosa

Joaquín R. Otero-Asman; Ana Sánchez-Jiménez; Karlijn C. Bastiaansen; Sarah Wettstadt; Cristina Civantos; Alicia García-Puente; Wilbert Bitter; María A. Llamas

doi:10.1016/j.isci.2023.107216

The Prc and CtpA proteases modulate cell-surface signaling activity and virulence in Pseudomonas aeruginosa

Joaquín R. Otero-Asman
, Ana Sánchez-Jiménez
, Karlijn C. Bastiaansen
, Sarah Wettstadt
, Cristina Civantos
, Alicia García-Puente
, Wilbert Bitter
, María A. Llamas^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Cell-surface signaling (CSS) is a signal transfer system of Gram-negative bacteria that produces the activation of an extracytoplasmic function σ factor (σ^ECF) in the cytosol in response to an extracellular signal. Activation requires the regulated and sequential proteolysis of the σ^ECF-associated anti-σ factor, and the function of the Prc and RseP proteases. In this work, we have identified another protease that modulates CSS activity, namely the periplasmic carboxyl-terminal processing protease CtpA. CtpA functions upstream of Prc in the proteolytic cascade and seems to prevent the Prc-mediated proteolysis of the CSS anti-σ factor. Importantly, using zebrafish embryos and the A549 lung epithelial cell line as hosts, we show that mutants in the rseP and ctpA proteases of the human pathogen Pseudomonas aeruginosa are considerably attenuated in virulence while the prc mutation increases virulence likely by enhancing the production of membrane vesicles.

Original language	English
Article number	107216
Pages (from-to)	1-16
Number of pages	17
Journal	iScience
Volume	26
Issue number	7
Early online date	26 Jun 2023
DOIs	https://doi.org/10.1016/j.isci.2023.107216
Publication status	Published - 21 Jul 2023

Bibliographical note

Funding Information:
We thank A. Ocampo and F. Madrazo (Hospital Universitario Marqués de Valdecilla) for assistance with A549 cytotoxicity assays and time-lapse imaging, and K. K. Jim for assistance with the zebrafish embryo infections. This work was funded by MCIN / AEI /10.13039/501100011033 Spanish agency with projects BIO2017-83763-P and PID2020-115682GB-I00 , and the PAIDI-2020 program of Junta de Andalucía (Spain) with project P18-FR-1621. JOA was supported by the Spanish Ministry of Economy through an FPI fellowship ( BES-2013-066301 ).

Publisher Copyright:
© 2023 The Author(s)

Funding

We thank A. Ocampo and F. Madrazo (Hospital Universitario Marqués de Valdecilla) for assistance with A549 cytotoxicity assays and time-lapse imaging, and K. K. Jim for assistance with the zebrafish embryo infections. This work was funded by MCIN / AEI /10.13039/501100011033 Spanish agency with projects BIO2017-83763-P and PID2020-115682GB-I00 , and the PAIDI-2020 program of Junta de Andalucía (Spain) with project P18-FR-1621. JOA was supported by the Spanish Ministry of Economy through an FPI fellowship ( BES-2013-066301 ).

Keywords

Biochemistry
Biological sciences
Microbiology
Natural sciences

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10.1016/j.isci.2023.107216

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Cite this

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title = "The Prc and CtpA proteases modulate cell-surface signaling activity and virulence in Pseudomonas aeruginosa",

abstract = "Cell-surface signaling (CSS) is a signal transfer system of Gram-negative bacteria that produces the activation of an extracytoplasmic function σ factor (σECF) in the cytosol in response to an extracellular signal. Activation requires the regulated and sequential proteolysis of the σECF-associated anti-σ factor, and the function of the Prc and RseP proteases. In this work, we have identified another protease that modulates CSS activity, namely the periplasmic carboxyl-terminal processing protease CtpA. CtpA functions upstream of Prc in the proteolytic cascade and seems to prevent the Prc-mediated proteolysis of the CSS anti-σ factor. Importantly, using zebrafish embryos and the A549 lung epithelial cell line as hosts, we show that mutants in the rseP and ctpA proteases of the human pathogen Pseudomonas aeruginosa are considerably attenuated in virulence while the prc mutation increases virulence likely by enhancing the production of membrane vesicles.",

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note = "Funding Information: We thank A. Ocampo and F. Madrazo (Hospital Universitario Marqu{\'e}s de Valdecilla) for assistance with A549 cytotoxicity assays and time-lapse imaging, and K. K. Jim for assistance with the zebrafish embryo infections. This work was funded by MCIN / AEI /10.13039/501100011033 Spanish agency with projects BIO2017-83763-P and PID2020-115682GB-I00 , and the PAIDI-2020 program of Junta de Andaluc{\'i}a (Spain) with project P18-FR-1621. JOA was supported by the Spanish Ministry of Economy through an FPI fellowship ( BES-2013-066301 ). Publisher Copyright: {\textcopyright} 2023 The Author(s)",

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AU - Otero-Asman, Joaquín R.

AU - Sánchez-Jiménez, Ana

AU - Bastiaansen, Karlijn C.

AU - Wettstadt, Sarah

AU - Civantos, Cristina

AU - García-Puente, Alicia

AU - Bitter, Wilbert

AU - Llamas, María A.

N1 - Funding Information: We thank A. Ocampo and F. Madrazo (Hospital Universitario Marqués de Valdecilla) for assistance with A549 cytotoxicity assays and time-lapse imaging, and K. K. Jim for assistance with the zebrafish embryo infections. This work was funded by MCIN / AEI /10.13039/501100011033 Spanish agency with projects BIO2017-83763-P and PID2020-115682GB-I00 , and the PAIDI-2020 program of Junta de Andalucía (Spain) with project P18-FR-1621. JOA was supported by the Spanish Ministry of Economy through an FPI fellowship ( BES-2013-066301 ). Publisher Copyright: © 2023 The Author(s)

PY - 2023/7/21

Y1 - 2023/7/21

N2 - Cell-surface signaling (CSS) is a signal transfer system of Gram-negative bacteria that produces the activation of an extracytoplasmic function σ factor (σECF) in the cytosol in response to an extracellular signal. Activation requires the regulated and sequential proteolysis of the σECF-associated anti-σ factor, and the function of the Prc and RseP proteases. In this work, we have identified another protease that modulates CSS activity, namely the periplasmic carboxyl-terminal processing protease CtpA. CtpA functions upstream of Prc in the proteolytic cascade and seems to prevent the Prc-mediated proteolysis of the CSS anti-σ factor. Importantly, using zebrafish embryos and the A549 lung epithelial cell line as hosts, we show that mutants in the rseP and ctpA proteases of the human pathogen Pseudomonas aeruginosa are considerably attenuated in virulence while the prc mutation increases virulence likely by enhancing the production of membrane vesicles.

AB - Cell-surface signaling (CSS) is a signal transfer system of Gram-negative bacteria that produces the activation of an extracytoplasmic function σ factor (σECF) in the cytosol in response to an extracellular signal. Activation requires the regulated and sequential proteolysis of the σECF-associated anti-σ factor, and the function of the Prc and RseP proteases. In this work, we have identified another protease that modulates CSS activity, namely the periplasmic carboxyl-terminal processing protease CtpA. CtpA functions upstream of Prc in the proteolytic cascade and seems to prevent the Prc-mediated proteolysis of the CSS anti-σ factor. Importantly, using zebrafish embryos and the A549 lung epithelial cell line as hosts, we show that mutants in the rseP and ctpA proteases of the human pathogen Pseudomonas aeruginosa are considerably attenuated in virulence while the prc mutation increases virulence likely by enhancing the production of membrane vesicles.

KW - Biochemistry

KW - Biological sciences

KW - Microbiology

KW - Natural sciences

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AN - SCOPUS:85164363559

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M1 - 107216

ER -

The Prc and CtpA proteases modulate cell-surface signaling activity and virulence in Pseudomonas aeruginosa

Abstract

Bibliographical note

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Keywords

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