TY - JOUR
T1 - The Prc and CtpA proteases modulate cell-surface signaling activity and virulence in Pseudomonas aeruginosa
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
UR - http://www.scopus.com/inward/record.url?scp=85164363559&partnerID=8YFLogxK
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U2 - https://doi.org/10.1016/j.isci.2023.107216
DO - https://doi.org/10.1016/j.isci.2023.107216
M3 - Article
C2 - 37534181
SN - 2589-0042
VL - 26
SP - 1
EP - 16
JO - iScience
JF - iScience
IS - 7
M1 - 107216
ER -