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铜绿假单胞菌利用丙二酸盐会影响群体感应和毒力,并导致形成矿化的生物膜样结构。

Malonate utilization by Pseudomonas aeruginosa affects quorum-sensing and virulence and leads to formation of mineralized biofilm-like structures.

机构信息

Department of Biological Sciences, Texas Tech University, Lubbock, TX, USA.

Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.

出版信息

Mol Microbiol. 2021 Aug;116(2):516-537. doi: 10.1111/mmi.14729. Epub 2021 May 18.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that uses malonate among its many carbon sources. We recently reported that, when grown in blood from trauma patients, P. aeruginosa expression of malonate utilization genes was upregulated. In this study, we explored the role of malonate utilization and its contribution to P. aeruginosa virulence. We grew P. aeruginosa strain PA14 in M9 minimal medium containing malonate (MM9) or glycerol (GM9) as a sole carbon source and assessed the effect of the growth on quorum sensing, virulence factors, and antibiotic resistance. Growth of PA14 in MM9, compared to GM9, reduced the production of elastases, rhamnolipids, and pyoverdine; enhanced the production of pyocyanin and catalase; and increased its sensitivity to norfloxacin. Growth in MM9 decreased extracellular levels of N-acylhomoserine lactone autoinducers, an effect likely associated with increased pH of the culture medium; but had little effect on extracellular levels of PQS. At 18 hr of growth in MM9, PA14 formed biofilm-like structures or aggregates that were associated with biomineralization, which was related to increased pH of the culture medium. These results suggest that malonate significantly impacts P. aeruginosa pathogenesis by influencing the quorum sensing systems, the production of virulence factors, biofilm formation, and antibiotic resistance.

摘要

铜绿假单胞菌是一种机会性病原体,它使用丙二酸盐作为其多种碳源之一。我们最近报道称,当在创伤患者的血液中生长时,铜绿假单胞菌利用丙二酸盐的基因表达被上调。在这项研究中,我们探讨了丙二酸盐利用的作用及其对铜绿假单胞菌毒力的贡献。我们在含有丙二酸盐(MM9)或甘油(GM9)的 M9 最小培养基中培养铜绿假单胞菌菌株 PA14 作为唯一的碳源,并评估了生长对群体感应、毒力因子和抗生素耐药性的影响。与 GM9 相比,PA14 在 MM9 中的生长减少了弹性蛋白酶、鼠李糖脂和吡咯喹啉的产生;增强了绿脓菌素和过氧化氢酶的产生;并增加了其对诺氟沙星的敏感性。在 MM9 中生长降低了 N-酰基高丝氨酸内酯自诱导物的细胞外水平,这种影响可能与培养基 pH 值的增加有关;但对 PQS 的细胞外水平几乎没有影响。在 MM9 中生长 18 小时后,PA14 形成了类似于生物膜的结构或聚集体,这与生物矿化有关,而生物矿化与培养基 pH 值的增加有关。这些结果表明,丙二酸盐通过影响群体感应系统、毒力因子的产生、生物膜形成和抗生素耐药性,显著影响铜绿假单胞菌的发病机制。

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