Levofloxacin-Induced Insulin Aggregation: Biophysical and Computational Insights into Amyloidogenic Potential
Abstract
Protein misfolding, a hallmark of conformational diseases known as proteinopathies, arises when hydrophobic regions of proteins are exposed, leading to aggregation, loss of functionality and potential cytotoxicity. With the increasing prevalence of multidrug-resistant bacteria, repurposing antibiotics has gained attention for therapeutic applications beyond their conventional use. In this study, we investigated the amyloidogenic and anti-amyloidogenic potential of levofloxacin (LFX) using human insulin (HI) as a model, given its propensity to aggregate at injection sites in diabetes patients. Using various biophysical techniques, we observed a concentration-dependent increase in light scattering (LS) intensity and a corresponding rise in Thioflavin T (ThT) fluorescence intensity in the presence of LFX, indicating enhanced amyloid formation. Time-dependent ThT measurements revealed a shortened lag phase and a higher apparent rate constant for HI fibrillation under LFX exposure. Circular dichroism (CD) spectra showed a negative peak at 218 nm, signifying a transition to [Formula: see text]-sheet-rich structures, consistent with amyloid formation. Complementary in silico analyses corroborated these findings, with DSSP-based secondary structure analysis and Ramachandran plots confirming significant [Formula: see text]-sheet enrichment induced by LFX. These results suggest that LFX promotes HI aggregation, raising important implications for diabetic patients where LFX may…
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