West China Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China; National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China; Department of Phamacy, the 78th Group Army Hospital of Chinese PLA, Mudanjiang, Heilongjiang, China.
West China Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Genomics. 2023 Mar;115(2):110590. doi: 10.1016/j.ygeno.2023.110590. Epub 2023 Mar 1.
The role of peptidoglycan-associated lipoprotein (Pal) in A. baumannii pathogenesis remains unclear. Here, we illustrated its role by constructing a pal deficient A. baumannii mutant and its complementary strain.Transcriptome analysis of the WT and pal mutant revealed a total of 596 differentially expressed genes. Gene Ontology analysis revealed that pal deficiency caused the downregulation of genes related to material transport and metabolic processes. The pal mutant showed a slower growth and was sensitive to detergent and serum killing compared to WT strain, whereas, the complemented pal mutant showed rescued phenotype. The pal mutant caused decreased mortality in mice pneumonia infection compared to WT strain, while the complemented pal mutant showed increased mortality. Mice immunized with recombinant Pal showed 40% protection against A. baumannii-mediated pneumonia. Collectively, these data indicate Pal is a virulence factor of A. baumannii and may serve as a potential target for preventive or therapeutic interventions.
肽聚糖相关脂蛋白(Pal)在鲍曼不动杆菌发病机制中的作用尚不清楚。在这里,我们通过构建 pal 缺陷型鲍曼不动杆菌突变体及其互补菌株来阐明其作用。WT 和 pal 突变体的转录组分析共发现了 596 个差异表达基因。GO 分析表明,pal 缺失导致与物质转运和代谢过程相关的基因下调。与 WT 菌株相比,pal 突变体的生长速度较慢,对去污剂和血清杀伤敏感,而互补 pal 突变体则表现出挽救表型。Pal 突变体引起的小鼠肺炎感染死亡率低于 WT 菌株,而互补 pal 突变体则导致死亡率增加。用重组 Pal 免疫的小鼠对鲍曼不动杆菌介导的肺炎有 40%的保护作用。综上所述,这些数据表明 Pal 是鲍曼不动杆菌的毒力因子,可能成为预防或治疗干预的潜在靶点。