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
Affiliations
Joaquín R. Otero-Asman
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain
Ana Sánchez-Jiménez
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain
Karlijn C. Bastiaansen
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain; Department of Medical Microbiology and Infection Control, Amsterdam University medical centres, location VU University, 1081 HV Amsterdam, The Netherlands
Sarah Wettstadt
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain
Cristina Civantos
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain
Alicia García-Puente
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain
Wilbert Bitter
Department of Medical Microbiology and Infection Control, Amsterdam University medical centres, location VU University, 1081 HV Amsterdam, The Netherlands
María A. Llamas
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain; Corresponding author
Summary: 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.
