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近年来,针对铜绿假单胞菌感染的治疗靶点的鉴定和治疗策略的发展取得了进展。

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections.

机构信息

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, 78350, France.

Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, 1011, Switzerland.

出版信息

BMC Microbiol. 2023 Mar 30;23(1):86. doi: 10.1186/s12866-023-02832-x.

Abstract

The opportunistic human pathogen Pseudomonas aeruginosa is the causal agent of a wide variety of infections. This non-fermentative Gram-negative bacillus can colonize zones where the skin barrier is weakened, such as wounds or burns. It also causes infections of the urinary tract, respiratory system or bloodstream. P. aeruginosa infections are common in hospitalized patients for which multidrug-resistant, respectively extensively drug-resistant isolates can be a strong contributor to a high rate of in-hospital mortality. Moreover, chronic respiratory system infections of cystic fibrosis patients are especially concerning, since very tedious to treat. P. aeruginosa exploits diverse cell-associated and secreted virulence factors, which play essential roles in its pathogenesis. Those factors encompass carbohydrate-binding proteins, quorum sensing that monitor the production of extracellular products, genes conferring extensive drug resistance, and a secretion system to deliver effectors to kill competitors or subvert host essential functions. In this article, we highlight recent advances in the understanding of P. aeruginosa pathogenicity and virulence as well as efforts for the identification of new drug targets and the development of new therapeutic strategies against P. aeruginosa infections. These recent advances provide innovative and promising strategies to circumvent infection caused by this important human pathogen.

摘要

机会性病原体铜绿假单胞菌是多种感染的病原体。这种非发酵革兰氏阴性杆菌可以定植于皮肤屏障减弱的区域,如伤口或烧伤。它还会引起尿路感染、呼吸系统或血液系统感染。在住院患者中,铜绿假单胞菌感染很常见,而多药耐药性或广泛耐药性分离株可能是导致高住院死亡率的重要因素。此外,囊性纤维化患者的慢性呼吸系统感染尤其令人担忧,因为治疗非常繁琐。铜绿假单胞菌利用多种细胞相关和分泌的毒力因子,这些因子在其发病机制中起着至关重要的作用。这些因子包括碳水化合物结合蛋白、群体感应,以监测细胞外产物的产生、赋予广泛耐药性的基因,以及一个分泌系统,将效应物输送到杀死竞争者或颠覆宿主基本功能。在本文中,我们强调了对铜绿假单胞菌致病性和毒力的理解方面的最新进展,以及鉴定新的药物靶点和开发针对铜绿假单胞菌感染的新治疗策略的努力。这些最新进展为规避这种重要人类病原体引起的感染提供了创新和有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a78a/10061973/0b7dac7d822e/12866_2023_2832_Fig1_HTML.jpg

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