Molecular dynamics simulation studies on uptake of fipronil sulfone by gut microbiome and its influence on risk for cause of Parkinson’s disease

ABSTRACT

Biotransformation of Fipronil forms three metabolites: fipronil sulfone, fipronil sulfide and fipronil desulfinyl. Among the triad of metabolites, fipronil sulfone exhibits quantitatively predominant production. Research on Fipronil and its relationship with Parkinson's disease (PD) has exclusively focused on the parent compound (fipronil), with no consideration given to its metabolites.

We aim to investigate the effect of fipronil sulfone, on gut bacterial proteins involved in metabolite production, adversely affect patients with Parkinson’s disease.

The proteins Diaminopimelate epimerase (Q88V90) (DapF) from Lactobacillus sp., and.

Tyrosine Decarboxylase (P0DTQ4) (TDC) from Enterococcus sp. are involved in cellular mechanisms help bacteria maintain a normal functional state & cell population to produce metabolites.

The interaction of FS with DapF and TDC for each bacterial species was simulated. A concentration-based simulation was performed for 100 ns at 92 mg/L, half the LD50 value (184 mg/L) of Fipronil sulfone. The values of molecular simulation analysis of TDC and DapF respectively were: RMSD = 4.9846 nm & 2.0648 nm and RMSF = 1.788071 nm & 1.237829 nm.

The aforementioned interaction studies indicate conformation change in the protein structures of DapF and TDC could potentially inhibit the functioning of the bacteria, thereby reducing amount of metabolites produced possibly influencing Parkinson’s Disease.

Highlights

• Fipronil is metabolised by the human body into Fipronil sulfone (FPS) which is potentially more toxic than its parent compounds.

• FPS binds to proteins that are involved in essential biochemical pathways that are responsible for the survival or production of neurotransmitters.

• FPS shows strong binding to these proteins possibly leading to a change in the 3D structure which would indicate the compromise in the functionality of these proteins.

• This way, due to the failure of survival or an essential pathway being blocked, the amount of neurotransmitters produced could eventually reduce and affect the enteric nervous system, leading to worsening the symptoms of PD.

KEYWORDS:

• Enterococcus faecalis
• Lactobacillus plantarum
• pesticides
• Fipronil sulphone
• Parkinson’s Disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author’s contributions

The authors confirm contribution to the paper as follows: AB, AM, SS: Collected data, Analysed and interpreted results, Performed the experiments, and Drafted the manuscript. SS: Conceptualised the idea, Designed the analysis, Supervised the study and Edited the manuscript and Communication. All authors reviewed the results and approved the final version of the manuscript.