Development of an effective fluorescence probe for discovery of aminopeptidase inhibitors to suppress biofilm formation.
Tianhu ZhaoJian ZhangMaomao TangLuyan Z MaXiaoguang LeiPublished in: The Journal of antibiotics (2019)
The human pathogen Pseudomonas aeruginosa can easily form biofilms. The extracellular matrix produced by the bacterial cells acts as a physical barrier to hinder the antibiotics treatment. It is necessary to destroy the biofilm in order to improve the efficacy of antibiotics. However, it has been a significant challenge to develop effective small molecules targeting the components of biofilm matrix. In this study, we report the development of a new effective fluorescence probe that could be used in the high throughput screening to identify novel small molecule inhibitors targeting the most abundant component in the biofilm formation: P. aeruginosa aminopeptidase (PaAP). Through screening of an in-house chemical library, a commercially available drug, balsalazide, has been identified as a novel PaAP inhibitor, which exhibited remarkable anti-biofilm effect. Our study indicated that the newly developed fluorescence probe is applicable in exploring new aminopeptidase inhibitors, and it also warrants further investigation of balsalazide as a new anti-biofilm agent to treat P. aeruginosa infection in combination with known antibiotics.
Keyphrases
- biofilm formation
- pseudomonas aeruginosa
- candida albicans
- staphylococcus aureus
- small molecule
- cystic fibrosis
- extracellular matrix
- escherichia coli
- living cells
- single molecule
- acinetobacter baumannii
- quantum dots
- induced apoptosis
- mental health
- cancer therapy
- energy transfer
- emergency department
- endothelial cells
- drug delivery
- high throughput
- fluorescent probe
- cell cycle arrest
- drug resistant
- endoplasmic reticulum stress