Evaluation of teixobactin derivatives as potential antimicrobial agents.

Abstract

Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) are on the World Health Organization (WHO) high priority list of pathogens that require serious attention. Therefore, the need for novel class of compounds is vital in overcoming this problem. Teixobactin is a new class of antibiotic that has exhibited antimicrobial activity against resistant bacteria. In this study we are expanding the investigation of teixobactin derivatives against clinically relevant bacterial isolates from South African patients. The minimum inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), the serum effect on the MIC’s and the time kill kinetics studies of three of our synthesized teixobactin derivatives 3, 4 and 5 were ascertained by broth microdilution according to the CLSI 2017 guidelines. Haemolysis on red blood cells (RBCs) and cytotoxicity on peripheral blood mononuclear cells (PBMCs) were performed to investigate the safety of these derivatives. MIC’s of the teixobactin derivatives against ATCC reference strains were between 4-64 µg/ml (3), 2-64 µg/ml (4) and 0.5-64 µg/ml (5). The MIC’s for MRSA were 32 µg/ml for (3), 2-4 µg/ml for (4) and 2-4 µg/ml for (5) whilst the MIC’s obtained for VRE’s were 8-16 μg/ml for (3), 4 μg/ml for (4) and 2-16 μg/ml for (5). 50% human serum had no effect on the MIC’s. All these derivatives did not show any effect on cell viability at their effective concentration. Teixobactin derivatives (3, 4 and 5) were capable of inhibiting bacterial growth in drug resistant bacteria and thus serve as potential antimicrobial agents.