Silver Nanoparticle Inhibited Levofloxacin Resistance Development in Staphylococcus aureus

Silver nanoparticle (AgNP) has been reported to have synergistic effects with several antibiotics. This study investigated the interaction between 4-nm AgNP and levofloxacin and its potential to inhibit antibiotic resistance development. The synergy of AgNP and levofloxacin was assessed using a checkerboard assay. The effect of AgNP on the development of levofloxacin resistance was investigated via serially exposing S. aureus ATCC 29213 to the sub-minimal inhibitory concentration (MIC) values of levofloxacin under the absence or presence of AgNP at 0.001 and 0.01 mg/L for 14 days. The interaction of AgNP with LexA and RecA was assessed in silico using molecular docking. The MIC values of AgNP and levofloxacin were identical when alone or in combination, 0.04 mg/L and 0.0125 mg/L, respectively, indicating no synergistic effect. MIC of AgNP increased only 2 folds from 0.04 mg/L to 0.08 mg/L after 14 days of sub-MIC serial exposure of S. aureus to AgNP. Meanwhile, the MIC of levofloxacin increased 128 folds from 0.125 to 16 mg/L after 14-day exposure to sub-MIC values of levofloxacin alone or in combination with 0.001 mg/L AgNP. Interestingly, when combining levofloxacin with 0.01 mg/L AgNP, the MIC of levofloxacin increased only 4 folds from 0.125 to 0.5 mg/L. Molecular docking showed no direct interaction between AgNP and RecA-LexA. AgNP did not interact with levofloxacin but reduced the levofloxacin resistance development rate. Additionally, AgNP did not trigger resistance development. This suggested the potential therapeutic usage of AgNP alone or in combination with antibiotics.