Evaluation of the inhibitory effect of caffeic acid and gallic acid on tetR and tetM efflux pumps mediating tetracycline resistance in Streptococcus sp., using computational approach

Background: Emergence of tet-efflux pump based tetracycline resistance in Streptococcus spp. is quite alarming worldwide posing a serious impediment in the treatment process. This leads to the search of novel target proteins to develop newer drugs against tetracycline resistant Streptococci spp. Caffeic acid and gallic acid being vital phenolic compounds might target the tet based efflux pumps. The aim of the present study is thus to explore the inhibitory potential of caffeic acid and gallic acid against tet-efflux pump mediated tetracycline resistant Streptococci spp. Materials and methods: 3D structure of tetR and tetM was retrieved from the PDB data bank with further optimization of both the protein and ligands. In-silico inhibitory potential of the selected ligands against tetR and tetM was done by AutoDock 2.0 and was visualized with Accelrys Discovery Studio Visualizer tool with the assessment of the molecular properties of the ligands by molinspiration calculations and further assessment for their drug likeliness. Results: Caffeic acid seem to possess promising inhibitory activity to target tetR and tetM with a promising binding energy of -5.93 and -4.6 Kcal/mol with 7 and 6 hydrogen bonds respectively. Molinspiration assessments showed zero violations with TPSA values < 140 angstrom towards the best oral bioavailability. Conclusion: The findings of the study emphasize that caffeic acid and gallic acid to possess a promising inhibitory effect against tetR and tetM of Streptococci spp. suggesting caffeic acid and gallic acid as the best drug candidates to combat tet-pump mediated tetracycline resistance with further in-vivo validation targeting the same. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.