Abstract
A rapid method to determine drug resistance in bacteria based on mass spectrometry is presented. In it, a mass spectrum of an intact microorganism grown in drug-containing stable isotope-labeled media is compared with a mass spectrum of the intact microorganism grown in non-labeled media without the drug present. Drug resistance is determined by predicting characteristic mass shifts of one or more microorganism biomarkers using bioinformatics algorithms. Observing such characteristic mass shifts indicates that the microorganism is viable even in the presence of the drug, thus incorporating the isotopic label into characteristic biomarker molecules. The performance of the method is illustrated on the example of intact E. coli, grown in control (unlabeled) and 13C-labeled media, and analyzed by MALDI TOF MS. Algorithms for data analysis are presented as well.
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Acknowledgments
The research described here was supported by internal JHU/APL funding. The authors thank J. Crookston, K. Kerbel, H. Le, R. Quizon, and K. Suslow (JHU/APL) for help in growing the microorganisms used in this study.
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This paper is dedicated to Dr. Catherine Fenselau, recipient of the 2012 ASMS Award for Distinguished Contribution in Mass Spectrometry.
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Demirev, P.A., Hagan, N.S., Antoine, M.D. et al. Establishing Drug Resistance in Microorganisms by Mass Spectrometry. J. Am. Soc. Mass Spectrom. 24, 1194–1201 (2013). https://doi.org/10.1007/s13361-013-0609-x
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DOI: https://doi.org/10.1007/s13361-013-0609-x