Unraveling antimicrobial resistance using metabolomics.

The emergence of antimicrobial resistance (AMR) in bacterial pathogens represents a global health threat. The metabolic state of bacteria is associated with a range of genetic and phenotypic resistance mechanisms. This review provides an overview of the roles of metabolic processes that are associated with AMR mechanisms, including energy production, cell wall synthesis, cell-cell communication, and bacterial growth. These metabolic processes can be targeted with the aim of re-sensitizing resistant pathogens to antibiotic treatments. We discuss how state-of-the-art metabolomics approaches can be used for comprehensive analysis of microbial AMR-related metabolism, which may facilitate the discovery of novel drug targets and treatment strategies.

Simultaneous analysis of E1 and E2 by LC-MS/MS in healthy volunteers: estimation of reference intervals and comparison with a conventional E2 immunoassay.

Monitoring estrogen levels, especially estradiol (E2), is amongst others important for determining menopausal status and guidance of breast cancer treatment. We validated a serum E2 and estrone (E1) liquid chromatography tandem-mass spectrometry assay (LC-MS/MS) suitable for quantitation in human subjects. In addition, we compared our method with an E2 immunoassay (IA) and established preliminary reference values. Validation parameters were within the predetermined acceptance criteria. Assay linearity ranges were 4-1500 pmol/L for E1 and 4-2500 pmol/L for E2. Imprecision ranged from 7.4 to 9.6%. The lower limit of quantitation for E2 (8.0 pmol/L) was 11.4 times lower than the IA. The method comparison revealed differences in E2 quantitation up to 155% between both methods. The method allowed quantitation of E1 in all healthy volunteers, while E2 could not be detected in 95% versus 40% of the post-menopausal women using IA and LC-MS/MS, respectively. Male, pre-, peri- and postmenopausal female reference values were estimated. An LC-MS/MS based method combining E1 and E2 analysis was validated with superior E2 analytical sensitivity when compared to the IA.