Activity of Fluoroquinolones and Proton Pump Inhibitors against Resistant Oral Bacterial Biofilms, in silico and in vitro Analysis

Abstract

Oral bacterial infections are a great health concern worldwide especially in diabetic patients. Emergence of antimicrobial resistance with reference to biofilms in oral cavity is of great concern. We investigated antibiotics combination with proton pump inhibitors against oral clinical isolates. The strains were identified as Staphylococcus epidermidis and Staphylococcus aureus by the 16S rRNA gene sequencing. In molecular docking, ciprofloxacin, levofloxacin, and omeprazole best fit to active pockets of transcriptional regulators 4BXI and 3QP1. None of the proton pump inhibitors were active against S. epidermidis, whereas omeprazole showed significant inhibition (MIC 3.9 μg/ml). Fluoroquinolones were active against both S. epidermidis and S. aureus. In combination analysis, a marked decrease in minimum inhibitory concentration was noticed with omeprazole (MIC 0.12 μg/ml). In antiquorum sensing experiments, a significant inhibitory zone was shown for all fluoroquinolones (14–20 mm), whereas among proton pump inhibitors, only omeprazole (12 ± 0.12 mm) was active against Chromobacterium violaceum. In combination analysis, a moderate increase in antiquorum sensing activity was recorded for ciprofloxacin, ofloxacin, and proton pump inhibitors. Further, significant S. aureus biofilm eradication was recorded using of ciprofloxacin, levofloxacin, and omeprazole combination (78 ± 2.1%). The time-kill kinetic studies indicated a bactericidal effect by ciprofloxacin: levofloxacin: omeprazole combination over 24 hrs. It was concluded that fluoroquinolone combined with omeprazole could be an effective treatment option for eradicating oral bacterial biofilms.

Keywords

• antiquorum sensing
• molecular docking
• synergism
• fluoroquinolones
• proton pump inhibitors