西班牙巴塞罗那科技学院Maria Lluch-Senar和Luis Serrano共同合作，近期取得重要工作进展。他们研究发现工程化活菌抑制小鼠肺部的铜绿假单胞菌感染并溶解气管导管生物膜。相关研究成果2023年1月19日在线发表于《自然—生物技术》杂志上。

据介绍，经过工程改造的活细菌可能为治疗肺部感染提供一种新的方式，肺部感染是全球性死亡的主要原因。

研究人员设计了一种基因组还原的人类肺部细菌（肺炎支原体），用于治疗呼吸机相关性肺炎，这是一种与铜绿假单胞菌生物膜相关的医院高死亡率疾病。在验证小鼠体内减毒肺炎支原体的生物安全性后，研究人员通过易位将四种转基因引入染色体，以实现杀菌和生物膜降解活性。在小鼠模型中，该工程菌株对急性铜绿假单胞菌肺部感染具有很高的疗效。

此外，研究人员证明，该工程菌株可以溶解呼吸机相关性肺炎患者气管内形成的生物膜，并与针对肽聚糖层的抗生素结合，以提高对革兰氏阳性和革兰氏阴性细菌的疗效。

总之，研究人员希望肺炎支原体工程菌株能够治疗呼吸道生物膜相关感染。

附：英文原文

Title: Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms

Author: Mazzolini, Rocco, Rodrguez-Arce, Irene, Fernndez-Barat, Laia, Piero-Lambea, Carlos, Garrido, Victoria, Rebollada-Merino, Agustn, Motos, Anna, Torres, Antoni, Grill, Maria Jess, Serrano, Luis, Lluch-Senar, Maria

Issue&Volume: 2023-01-19

Abstract: Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract.

DOI: 10.1038/s41587-022-01584-9

Source: https://www.nature.com/articles/s41587-022-01584-9