Investigating Antibiotic Resistance in \u3ci\u3eStaphylococcus aureus\u3c/i\u3e and \u3ci\u3eStreptococcus mitis-oralis\u3c/i\u3e by Nuclear Magnetic Resonance Based Metabolomics

Abstract

Metabolomics is rapidly growing in popularity as a valuable resource for drug discovery due to its ability to identify perturbations in metabolic pathways between healthy controls and drug treatment groups. Metabolomics can differentiate between different phenotypes resulting from genetic changes or in response to variations in environmental conditions. Conversely, genomics, transcriptomics, and proteomics can only provide insight into the outcome that could happen. Notably, metabolomics is commonly used to observe the effects of environmental stress on bacteria and between resistant and non-resistant strains of bacteria. The development of a protocol to grow Staphylococcus aureus in a blood-like environment was essential in identify the metabolic, growth, and survivability differences cause due to cultivation medium. The blood-like environment consist of tryptic soy broth without dextrose (TSB-DEX) with 55% Serum. Daptomycin-susceptible (DapS) and daptomycin-nonsusceptible (DapNS) strains of S. aureus were then cultured in the blood-like environment to identify metabolome differences. NMR and mass spectrometry were used in combination to provide a comprehensive characterization of metabolic perturbations. In this regards, adaptive metabolic differences between DapS and DapNS may be leveraged as potential therapeutic targets. NMR metabolomics was also used to characterize metabolic response for adaptive resistance strains of Streptococcus mitis-oralis to daptomycin. Advisor: Robert Power