QUORUM-SENSING INHIBITION BY FURANONE COMPOUNDS AND THERAPEUTIC EFFECTS ON PSEUDOMONAS AERUGINOSA KERATITIS RABBIT MODEL

Nowadays, the occurrence of multi-drug resistant microbial pathogens threatens the foundation upon which standard antibacterial treatment is based. Therefore, alternative treatment methods have been investigated. There is a new strategy to control infections that aim to affect and stop the adaptability of microbes to the host environment and prevent their communication with each other. A mechanism called Quorum Sensing (QS) is the communication between bacterial cells that rely on cell density and the concentration of specific signaling molecules. Inhibitors of QS are an advanced strategy discovered to decrease P. aeruginosa virulence. Based on previous studies and the proven effects of furanones as a quorum sensing inhibitor on pseudomonas infection, this study aimed to investigate the bacterial restriction effects of furanone compounds in P. aeruginosa keratitis rabbit model.

This study was an experimental research carried out at the Bezmialem Vakıf University Experimental Application and Research Center, Turkey. 

30 adult New Zealand white rabbits were used in this study. Commercially purchased synthetic Furanone C-30 was used due to its ability to inhibit biofilm formation and it was dissolved with 20% dimethyl sulfoxide (DMSO). Corneas of rabbits were intrastromally injected with P. aeruginosa. While control group had no treatment, other groups received various eye drops every hour starting one hour after P. aeruginosa inoculation: 50 mg/ml ceftazidime (A), 0.1 mg/ml, 0.2 mg/ml and 0.3 mg/ml Furanone (B), (C), (D) respectively and 20% DMSO (E). Then, rabbits were sacrificed 3 days later and corneas were collected. For clinical evaluation, slit lamp examination (SLE) of pathological changes in rabbit eyes was performed. Each of the five parameters was graded on a scale ranging from 0 (none) to a maximum of 4 (severe): injection, chemosis, hypopyon, corneal infiltrate, and corneal edema. As microbiological evaluation, quantitative colony count was used. Tissue samples were followed up for light microscopy and immunohistochemical examination was done. Anti-oxidant SOD-1 enzyme was calculated and Reactive Oxygen Species (ROS) was measured as biochemical evaluation.

In all evaluations, the therapeutic response in the antibiotic group was better than other groups. SLE score of Group C was significantly lowered compared to the control group (p=0.009). Histological evaluation shows that inflammation is decreased in B, C and D groups. Reactive Oxygen Species (ROS) values were significantly lower in group B (p=0.001) and C (p=0.01). And there was no statistical significance among Superoxide dismutase (SOD1) values and microbiological evaluation.

The comprehensive findings demonstrate that furanone showed an anti-inflammatory effect. However, its therapeutic effect has not been observed to be sufficient when compared to antibiotics. Further investigation is necessary to explore the protective effects and mechanism of furanones on pseudomonas keratitis.