title: Staying Alive: Measuring Intact Viable Microbes with Electrospray Ionization Mass Spectrometry.
abstract: Mass spectrometry has traditionally been the technology of choice for small molecule analysis, making significant inroads into metabolism, clinical diagnostics, and pharmacodynamics since the 1960s. In the mid-1980s, with the discovery of electrospray ionization (ESI) for biomolecule analysis, a new door opened for applications beyond small molecules. Initially, proteins were widely examined, followed by oligonucleotides and other nonvolatile molecules. Then in 1991, three intriguing studies reported using mass spectrometry to examine noncovalent protein complexes, results that have been expanded on for the last 25 years. Those experiments also raised the questions: How soft is ESI, and can it be used to examine even more complex interactions? Our lab addressed these questions with the analyses of viruses, which were initially tested for viability following electrospray ionization and their passage through a quadrupole mass analyzer by placing them on an active medium that would allow them to propagate. This observation has been replicated on multiple different systems, including experiments on an even bigger microbe, a spore. The question of analysis was also addressed in the early 2000s with charge detection mass spectrometry. This unique technology could simultaneously measure mass-to-charge and charge, allowing for the direct determination of the mass of a virus. More recent experiments on spores and enveloped viruses have given us insight into the range of mass spectrometry's capabilities (reaching 100 trillion Da), beginning to answer fundamental questions regarding the complexity of these organisms beyond proteins and genes, and how small molecules are integral to these supramolecular living structures. Graphical Abstract ᅟ.
authors.affiliation: Scripps Center for Metabolomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Forsberg
authors.affiliation: Scripps Center for Metabolomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.|School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Fang
authors.affiliation: Scripps Center for Metabolomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. siuzdak@scripps.edu.|Departments of Chemistry, Molecular and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. siuzdak@scripps.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
mesh_terms: D001419:Bacteria / Q000737:chemistry* / Q000166:cytology; D001424:Bacterial Infections / Q000382:microbiology; D004868:Equipment Failure; D006801:Humans; D050296:Microbial Viability; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*; D014777:Virus Diseases / Q000821:virology; D014780:Viruses / Q000737:chemistry*
keywords: Bacteria; Charge detection; Electrophoretic mobility; Intact; Mass spectrometry; Noncovalent interactions; Viability; Virus