Attenuation of Enterococcus faecalis biofilm formation by Rhodethrin: A combinatorial study with an antibiotic

The nosocomial pathogen Enterococcus faecalis critically implicated in the hospital environment. Its major virulence attributes biofilm formation and antibiotic resistance. The novel therapeutics are required to inhibit E. faecalis biofilm formation and virulence. Thus combinatorial and drug repurposing has been promising approaches to tackling biofilm-associated infections. Here, we have used a bacterium that produced indole terpenoid Rhodethrin (Rdn) with a combination of known antibiotic chloramphenicol (Chpl) against E. faecalis (ATCC 19433). The fractional inhibitory concentration index (FICI) values showed between 0.25 and 0.33 synergistic activities. The exopolysaccharides (EPSs) production significant decrease with Rdn (34.6 +/- 4.6%), Chpl (31.0 +/- 5.2%), and combination (Rdn-Chpl) (76.0 +/- 4.5%) (p > 0.05). However, the biofilm interruption can attenuate of total biofilm was shown with Rdn (39.7 +/- 5.1%), Chpl (32.6 +/- 4.7%), and Rdn-Chpl (69.0 +/- 5.3%), (p > 0.05). The microscopic observations reveal that the gradually unstructured biofilm architecture in E. faecalis. Furthermore, in silico, studies on biofilm-associated proteins (GelE, LuxS), virulence regulating (SprE), and cell division (FtsZ) have resulted in high and reasonable binding affinity, respectively. Thus, our results suggested that the synergism of Rdn-Chpl has the potential to function as a combinatorial antibiotic accelerates in treating vancomycin-resistant Enterococcus faecalis infections.

Automated summary

This study investigated the synergistic effect of the combination of indole terpenoid Rhodethrin and chloramphenicol against Enterococcus faecalis. The results showed that the combination had a synergistic effect in inhibiting biofilm formation, but had limited effect on biofilm interruption. In vitro studies indicated a high binding affinity between biofilm-associated proteins and the drugs used. These findings suggest that the combination of Rhodethrin and chloramphenicol has the potential to be used as a combinatorial antibiotic for treating vancomycin-resistant Enterococcus faecalis infections.