Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infection requiring ventilation, such as COVID-19. P. aeruginosa is also a widely-used model bacterium for all biological areas. In addition to continued, intense efforts in understanding bacterial pathogenesis of P. aeruginosa including virulence factors (LPS, quorum sensing, two-component systems, 6 type secretion systems, outer membrane vesicles (OMVs), CRISPR-Cas and their regulation), rapid progress has been made in further studying host-pathogen interaction, particularly host immune networks involving autophagy, inflammasome, non-coding RNAs, cGAS, etc. Furthermore, numerous technologic advances, such as bioinformatics, metabolomics, scRNA-seq, nanoparticles, drug screening, and phage therapy, have been used to improve our understanding of P. aeruginosa pathogenesis and host defense. Nevertheless, much remains to be uncovered about interactions between P. aeruginosa and host immune responses, including mechanisms of drug resistance by known or unannotated bacterial virulence factors as well as mammalian cell signaling pathways. The widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections, especially those caused by multi-drug resistance strains. Benefited from has advancing in research tools and technology, dissecting this pathogen’s feature has entered into molecular and mechanistic details as well as dynamic and holistic views. Herein, we comprehensively review the progress and discuss the current status of P. aeruginosa biophysical traits, behaviors, virulence factors, invasive regulators, and host defense patterns against its infection, which point out new directions for future investigation and add to the design of novel and/or alternative therapeutics to combat this clinically significant pathogen.

铜绿假单胞菌( P. aeruginosa ) 是一种革兰氏阴性机会致病菌，可感染患有囊性纤维化、烧伤、免疫缺陷、慢性阻塞性肺病 (COPD)、癌症和需要通气的严重感染（如 COVID-19）的患者。铜绿假单胞菌也是所有生物领域广泛使用的模型细菌。除了持续不断地努力了解铜绿假单胞菌的细菌发病机制，包括毒力因子（LPS、群体感应、双组分系统、6 种分泌系统、外膜囊泡 (OMV)、CRISPR-Cas 及其调控）、快速进一步研究宿主与病原体相互作用，特别是涉及自噬、炎症小体、非编码RNA、cGAS等的宿主免疫网络已取得进展。此外，生物信息学、代谢组学、scRNA-seq、纳米粒子、药物筛选和噬菌体治疗等众多技术进步已被用来提高我们对铜绿假单胞菌发病机制和宿主防御的理解。然而，关于铜绿假单胞菌和宿主免疫反应之间的相互作用，还有很多有待揭示，包括已知或未注释的细菌毒力因子以及哺乳动物细胞信号通路的耐药机制。抗生素的广泛使用和有效抗菌药物的缓慢发展带来了严峻的挑战，需要新的理论和实践平台来筛选和开发经过机制测试的新药来治疗顽固性感染，特别是由多重耐药菌株引起的感染。 得益于研究工具和技术的进步，对该病原体的特征的剖析已进入分子细节、机制细节以及动态和整体的观点。在此，我们对铜绿假单胞菌的生物物理性状、行为、毒力因子、侵袭调节因子以及宿主针对其感染的防御模式的研究现状进行了全面的回顾和讨论，为今后的研究指明了新的方向，并为新型铜绿假单胞菌的设计提供了新的思路。和/或替代疗法来对抗这种临床上重要的病原体。