Metabolomic Profiles of Multidrug-Resistant Salmonella Typhimurium from Humans, Bovine, and Porcine Hosts

SIMPLE SUMMARY: The global threat that is imposed by the resistance the pathogens develop to antimicrobial drugs is escalating. Tools to detect the resistance (with evidence on molecular and cellular outcomes) would reveal intricate mechanisms through which novel drugs could be developed. Approaches such as metabolomics, which involve metabolite detection, provide scientific evidence of metabolite expression of antimicrobial-resistant pathogens. The current study involved metabolomics of antimicrobial-resistant Salmonella Typhimurium collected from various hosts (human, porcine, bovine) and were exposed to antimicrobial drugs—ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline—as one set of the experiment. The same isolates were also cultured with no drug exposure as a comparison. There are certain pathways of metabolite expression that are impacted by drug exposure when compared to no drug exposure, meaning that the expressed metabolites could be potential targets for drug companies for the treatment of antimicrobial-resistant pathogens. ABSTRACT: Antimicrobial resistance (AMR) is a global public health threat, yet tools for detecting resistance patterns are limited and require advanced molecular methods. Metabolomic approaches produce metabolite profiles and help provide scientific evidence of differences in metabolite expressions between Salmonella Typhimurium from various hosts. This research aimed to evaluate the metabolomic profiles of S. Typhimurium associated with AMR and it compares profiles across various hosts. Three samples, each from bovine, porcine, and humans (total n = 9), were selectively chosen from an existing library to compare these nine isolates cultured under no drug exposure to the same isolates cultured in the presence of the antimicrobial drug panel ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfisoxazole, tetracycline). This was followed by metabolomic profiling using UPLC and GC–mass spectrometry. The results indicated that the metabolite regulation was affected by antibiotic exposure, irrespective of the host species. When exposed to antibiotics, 59.69% and 40.31% of metabolites had increased and decreased expressions, respectively. The most significantly regulated metabolic pathway was aminoacyl-tRNA biosynthesis, which demonstrated increased expressions of serine, aspartate, alanine, and citric acid. Metabolites that showed decreased expressions included glutamate and pyruvate. This pathway and associated metabolites have known AMR associations and could be targeted for new drug discoveries and diagnostic methods.