Mechanistic and biophysical insight into the inhibitory and disaggregase role of antibiotic moxifloxacin on human lysozyme amyloid formation.

Lysozyme amyloidosis is a systemic non-neuropathic disease caused by the accumulation of amyloids of mutant lysozyme. Presently, therapeutic interventions targeting lysozyme amyloidosis, remain elusive with only therapy available for lysozyme amyloidosis being supportive management. In this work, we examined the effects of moxifloxacin, a synthetic fluoroquinolone antibiotic on the amyloid formation of human lysozyme. The ability of moxifloxacin to interfere with lysozyme amyloid aggregation was examined using various biophysical methods like Rayleigh light scattering, Thioflavin T fluorescence assay, transmission electron microscopy and docking method. The reduction in scattering and ThT fluorescence along with extended lag phase in presence of moxifloxacin, suggest that the antibiotic inhibits and impedes the lysozyme fibrillation in concentration dependent manner. From ANS experiment, we deduce that moxifloxacin is able to decrease the hydrophobicity of the protein molecule thereby preventing aggregation. Our CD and DLS results show that moxifloxacin stabilizes the protein in its native monomeric structure, thus also showing retention of lytic activity upto 69% and inhibition of cytotoxicity at highest concentration of moxifloxacin. The molecular docking showed that moxifloxacin forms a stable complex of -7.6 kcal/mol binding energy and binds to the aggregation prone region of lysozyme thereby stabilising it and preventing aggregation. Moxifloxacin also showed disaggregase potential by disrupting fibrils and decreasing the β-sheet content of the fibrils. Our current study, thus highlight the anti-amyloid and disaggregase property of an antibiotic moxifloxacin and hence sheds light on the future of antibiotics against protein aggregation, a hallmark event in many neurodegenerative diseases.