Evaluation of teixobactin derivatives as potential antimicrobial agents.
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Date
2017
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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.
Description
Maters degree. University of KwaZulu-Natal, Durban.