Comparative analysis of SilA-laccase mediated degradation of ciprofloxacin, norfloxacin and ofloxacin and interpretation of the possible catalytic mechanism.

Fluoroquinolones (FQs) are the most commonly used antimicrobial drugs and regardless of their advantages in the healthcare sector, the pollution of these antimicrobial drugs in the environment has big concerns about human and environmental health. The presence of these antibiotic drugs even at the lowest concentrations in the environment has resulted in the emergence and spread of antibiotic resistance. Hence, it is necessary to remediate these pollutants from the environment. Previously alkaline laccase (SilA) from Streptomyces ipomoeae has been demonstrated to show degrading potentials against two of the FQs, Ciprofloxacin (CIP) and Norfloxacin (NOR); however, the molecular mechanism was not elucidated in detail. In this study, we have analyzed the possible molecular catalytic mechanism of FQ degrading SilA-laccase for the degradation of the FQs, CIP, NOR and Ofloxacin (OFL) using three-dimensional protein structure modeling, molecular docking and molecular dynamic (MD) studies. The comparative protein sequence analysis revealed the presence of tetrapeptide conserved catalytic motif, His102-X-His104-Gly105. After evaluating the active site of the enzyme in depth using CDD, COACH and S-site tools, we have identified the catalytic triad composed of three conserved amino acid residues, His102, Val103 and Tyr108 with which ligands interacted during the catalysis process. By analyzing the MD trajectories, it is revealed that the highest degradation potential of SilA is for CIP followed by NOR and OFL. Ultimately, this study provides the possible comparative catalytic mechanism for the degradation of CIP, NOR and OFL by the SilA enzyme.Communicated by Ramaswamy H. Sarma.

Fluoroquinolone antibiotics: Occurrence, mode of action, resistance, environmental detection, and remediation - A comprehensive review.

Antibiotics play an essential role in the medical healthcare world, but their widespread usage and high prevalence have posed negative environmental consequences. During the past few decades, various antibiotic drugs have been detected in aquatic and terrestrial ecosystems. Among them, the Fluoroquinolones (FQ) group is ubiquitous in the environment and has emerged as a major environmental pollutant. FQs are very significant, broad-spectrum antibiotics used in treating various pathogenic diseases of humans and animals. The most known and used FQs are ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, enrofloxacin, danofloxacin, and moxifloxacin. After human and animal administration, about 70% of these drugs are excreted out in unaltered form into the environment. Besides, wastewater discharge from pharmaceutical industries, hospitals, and agriculture runoff is the major contributor to the accumulation of FQs into the ecosystem. Their long-term presence in the environment creates selection pressure on microorganisms and contributes to the emergence of multi-drug-resistant bacteria. In addition to the resistance, these antibiotics also impose ecotoxicological effects on various animals and plant species. The presence of the fluorine atom in Fluoroquinolones makes them highly electronegative, strong, recalcitrant, and less compatible with microbial degradation. Many biological and chemical processes have been invented and successfully implemented during the past few decades for the elimination of these pollutants from the environment. This review provides a detailed overview of the classification, occurrence, distribution, and ecotoxicological effects of Fluoroquinolones. Their modes of action, resistance mechanism, detection and analysis methods, and remediation strategies have also been discussed in detail.