Molecular phenotyping approaches for the detection and monitoring of carbapenem-resistant Enterobacteriaceae by mass spectrometry

Abstract

Antimicrobial resistance is increasing in prevalence and there is a clear need for the development of rapid detection methods in clinical diagnostics. This review explores -omics studies utilising mass spectrometry to investigate the molecular phenotype associated with carbapenem resistance. Whilst the specific mechanisms of carbapenem resistance are well characterised, the resistant phenotype is poorly understood. Understanding how the acquisition of resistance affects cellular physiology and cell metabolism through molecular phenotyping is a necessary step towards detecting resistance by diagnostic means. In addition, this article examines the potential of mass spectrometry for the identification of resistance biomarkers through molecular profiling of bacteria. Developments in mass spectrometry platforms are expanding the biomarker-based diagnostic landscape. Targeted measures, such as high-resolution mass spectrometry coupled with chromatographic separation show considerable promise for the identification of molecular signatures and the development of a rapid diagnostic assay for the detection of carbapenem resistance.

Keywords: AMR, antimicrobial resistance; Antimicrobial resistance; CP, carbapenemase-producing; CR, carbapenem-resistance; CRE, carbapenem-resistant Enterobacteriaceae; CRO, carbapenem-resistant organism; DI, direct infusion; Enterobacteriaceae; FAME, fatty acid methyl ester; FTIR, Fourier-transform infrared spectroscopy; GC, gas chromatography; HILIC, hydrophilic interaction liquid chromatography; IM, ion mobility; KPC, Klebsiella pneumoniae carbapenemase; LC, liquid chromatography; Lipidomics; MALDI-TOF MS, matrix-assister laser desorption/ionisation-time of flight mass spectrometry; MIC, minimum inhibitory concentration; MOLI, metal oxide laser ionisation; MOS, metal oxide sensor; MRSA, methicillin-resistant Staphylococcus aureus; MS, mass spectrometry; Mass spectrometry; Metabolomics; NMR, nuclear magnetic resonance; OMV, outer membrane vesicle; PTM, post-translational modification; Proteomics; SESI, secondary electrospray ionisation; SIFT, selected-ion flow-tube; SPME, solid phase microextraction; TOF, time of flight.