Otero-Asman Joaquín R, Sánchez-Jiménez Ana, Bastiaansen Karlijn C, Wettstadt Sarah, Civantos Cristina, García-Puente Alicia, Bitter Wilbert, Llamas María A
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.
iScience. 2023 Jun 26;26(7):107216. doi: 10.1016/j.isci.2023.107216. eCollection 2023 Jul 21.
Cell-surface signaling (CSS) is a signal transfer system of Gram-negative bacteria that produces the activation of an extracytoplasmic function σ factor (σ) in the cytosol in response to an extracellular signal. Activation requires the regulated and sequential proteolysis of the σ-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 and proteases of the human pathogen are considerably attenuated in virulence while the mutation increases virulence likely by enhancing the production of membrane vesicles.
细胞表面信号传导（CSS）是革兰氏阴性菌的一种信号转导系统，它能响应细胞外信号，在细胞质中激活一种胞外功能σ因子（σ）。激活需要对与σ相关的抗σ因子进行有序的调控性蛋白水解，以及Prc和RseP蛋白酶的作用。在这项研究中，我们鉴定出了另一种调节CSS活性的蛋白酶，即周质羧基末端加工蛋白酶CtpA。CtpA在蛋白水解级联反应中位于Prc的上游，似乎能阻止Prc介导的CSS抗σ因子的蛋白水解。重要的是，我们以斑马鱼胚胎和A549肺上皮细胞系作为宿主，发现人类病原体的 和 蛋白酶突变体的毒力显著减弱，而 突变可能通过增强膜泡的产生而增加毒力。
