Quinic acid: a potential antibiofilm agent against clinical resistant Pseudomonas aeruginosa

Abstract

Background The biofilm state of pathogens facilitates antimicrobial resistance which makes difficult-to-treat infections. In this regard, it has been found that the compounds screened from plant extracts represent one category of the most promising antibiofilm agents. However, the antibiofilm activities and the active ingredients of plant extracts remain largely unexplored. In this background, the study is (1) to screen out the plant extracts with antibiofilm ability against Pseudomonas aeruginosa, and (2) to identify the active ingredients in the plant extracts and elucidate the underlying mechanism of the antibiofilm activities. Methods Micro-broth dilution method, in vitro biofilm model, LC–MS/MS analysis and P. aeruginosa-mouse infection model were adopted to assess the antibiofilm activity. GC–MS analysis was performed to detect the active ingredients in plasma. RNA-Seq, GO analysis, KEGG analysis and RT-qPCR were adopted to elucidate the underlying mechanism of antibiofilm activities against P. aeruginosa. Results Lonicerae Japonicae Flos (LJF) among 13 plants could exert significant inhibitory effects on bacterial biofilm formation, mobility and toxin release in vitro, and it could exert antibiofilm effect in vivo too. Moreover, quinic acid, as one metabolite of chlorogenic acid, was found as an active ingredient in LJF against the biofilm of P. aeruginosa. The active ingredient significantly inhibited EPS secretion in biofilm formation and maturity and could achieve synergistic antibiofilm effect with levofloxacin. It reduced the biofilm formation by regulating core targets in quorum sensing system. In GO process, it was found that the core targets were significantly enriched in multiple biological processes involving locomotion, chemotaxis and motility mediated by flagellum/cilium, which was related to KEGG pathways such as bacterial chemotaxis, oxidative phosphorylation, ribosome, biofilm formation, cyanoamino acid metabolism and quorum sensing. Finally, the binding of quinic acid with core targets rhlA, rhlR and rhlB were validated by molecular docking and RT-qPCR. Conclusions In summary, the study verified the in vitro and in vivo antibiofilm effects of LJF against P. aeruginosa and elucidated the active ingredients in LJF and its conceivable pharmacological mechanism, indicating that quinic acid could have the potential of an antibiofilm agent against P. aeruginosa and related infections. Graphic abstract

Extraction Optimization, Preliminary Identification, and Bioactivities in Corn Silk

“…While all the other six components have antibacterial activity and can ameliorate hyperglycemia activity. Studies have shown that quinic acid can inhibit the growth of a variety of bacteria [ 53 , 54 ], and it is a competitive inhibitor of α -amylase [ 55 ]. Chitosan/silver (CS/Ag) nanocomposite using rutin has antibacterial activity against B. subtilis [ 22 ]; in diabetic rat models, rutin can significantly reduce fasting blood sugar [ 56 ].…”

Nutritional anti-nutritional chemical composition and antioxidant activities of the leaves of the sea cliff dwelling species Limonium spathulatum (Desf.) Kuntze

“…Quinic acid is an organic acid mediating the ‘‘shikimate pathway’’ (shikimic acid pathway), which is a chief aromatic amino acid synthesis metabolic route exclusive to plants and microorganisms resulting in the formation of tryptophan (TRP), tyrosine (TYR), and phenylalanine (PHE) ( Averesch and Krömer, 2018 ). Quinic acid has important biological properties, including antioxidant ( Bursal et al., 2018 ), antimicrobial ( Lu et al., 2021 ; Bai et al., 2022 ) and anti HIV-1 ( Yazdi et al., 2019 ), and is a building block for the synthesis of several valuable secondary compounds, including coumaroyl and caffeoylquinic acid derivatives with significant biological activity in several drug-target areas ( Cheynier et al., 2012 ). A related compound of quinic acid, shikimic acid, was also detected in the ethanolic extract from L. spathulatum , is also key intermediate of the ‘‘shikimate pathway’’ and has a high pharmaceutical importance, such as being a precursor for the synthesis of oseltamivir (Tamiflu), the only drug against avian flu caused by the H5N1 virus ( Quiroz et al., 2014 ; Bai et al., 2022 ).…”

Calorie restriction remodels gut microbiota and suppresses tumorigenesis of colorectal cancer in mice

“…KEGG and COG databases were used to identify the potential functions of associated metabolic pathways. The metabolism of cyanoamino acids leads to an increase in the metabolism and production of intracellular signaling molecules and proteins, as well as the creation of biofilms ( 65 ). In gastric cancer, cyanoamino acid metabolism is disturbed and disorganized, which primarily manifests as upregulation of glycine levels and the downregulation of alanine levels ( 66 , 67 ).…”