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在囊性纤维化环境下建立的肺部感染模型中,D-氨基酸会影响铜绿假单胞菌生物膜和群体感应分子。

D-Amino acids affect Pseudomonas aeruginosa biofilm and quorum sensing molecules in lung infection models developed under a cystic fibrosis environment.

作者信息

Rosado-Rosa Joenisse M, Parmar Dharmeshkumar, Rubakhin Stanislav S, Shrout Joshua D, Sweedler Jonathan V

机构信息

Department of Chemistry, Beckman Institute for Advanced Science and Technology, Institute of Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.

Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA.

出版信息

Sci Rep. 2025 Jul 13;15(1):25328. doi: 10.1038/s41598-025-10519-8.

Abstract

Pseudomonas aeruginosa commonly infects immunocompromised patients, including those with cystic fibrosis (CF). These infections are difficult to treat due to a variety of factors including the ability of Pseudomonas aeruginosa to resist to antibiotic treatment in part due to formation of biofilms. D-amino acids have known biofilm-disruption and antibacterial properties in some bacteria including P. aeruginosa. However, this treatment remains underexplored especially for inhibiting biofilm biomass production under CF environments. We explore the effects of six individual D-amino acids (alanine, aspartic acid, tyrosine, glutamic acid, serine, and proline) on the quorum sensing signaling and biofilm biomass production of two strains: PAO1 and the CF isolate FRD1. The D-amino acid causing the most significant decrease in biofilm mass and a decrease in quorum sensing molecules was D-aspartic acid. Meanwhile D-glutamic acid and D-serine had the opposite effects with an increase in biofilm mass and increase in quorum sensing molecule abundance. D-proline also showed a decrease in quorum sensing signaling with a decrease in biofilm biomass. P. aeruginosa had a lower or delayed quorum sensing response in the presence of D-aspartic acid and the absence of its L- counterpart at 48 h, a potential therapeutic route to explore.

摘要

铜绿假单胞菌通常感染免疫功能低下的患者,包括患有囊性纤维化(CF)的患者。由于多种因素,包括铜绿假单胞菌形成生物膜从而对抗生素治疗产生耐药性的能力,这些感染难以治疗。D-氨基酸在包括铜绿假单胞菌在内的一些细菌中具有已知的生物膜破坏和抗菌特性。然而,这种治疗方法仍未得到充分探索,特别是在CF环境下抑制生物膜生物量的产生方面。我们研究了六种单个D-氨基酸(丙氨酸、天冬氨酸、酪氨酸、谷氨酸、丝氨酸和脯氨酸)对两种菌株:PAO1和CF分离株FRD1的群体感应信号传导和生物膜生物量产生的影响。导致生物膜量显著减少和群体感应分子减少的D-氨基酸是天冬氨酸。同时,D-谷氨酸和D-丝氨酸具有相反的效果,生物膜量增加且群体感应分子丰度增加。D-脯氨酸也显示出群体感应信号传导减少,生物膜生物量减少。在48小时时,在存在D-天冬氨酸且不存在其L-对应物的情况下,铜绿假单胞菌的群体感应反应较低或延迟,这是一条有待探索的潜在治疗途径。

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