AUTHOR=Solntceva Vera , Kostrzewa Markus , Larrouy-Maumus Gerald TITLE=Detection of Species-Specific Lipids by Routine MALDI TOF Mass Spectrometry to Unlock the Challenges of Microbial Identification and Antimicrobial Susceptibility Testing JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 10 - 2020 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.621452 DOI=10.3389/fcimb.2020.621452 ISSN=2235-2988 ABSTRACT=MALDI-TOF mass spectrometry has revolutionized clinical microbiology diagnostics by de-livering accurate, fast, and reliable identification of microorganisms. It is conventionally based on the detection of intracellular molecules, mainly ribosomal proteins, for identification at the species-level and/or genus-level. Nevertheless, for some microorganisms (e.g. for myco-bacteria) extensive protocols are necessary in order to extract intracellular proteins, and in some cases a protein-based approach cannot provide sufficient evidence to accurately identify the microorganisms within the same genus (e.g. Shigella sp. vs E. coli and the species of the M. tuberculosis complex). Consequently lipids, along with proteins are also molecules of in-terest. Lipids are ubiquitous, but their structural diversity delivers complementary information to the conventional protein-based clinical microbiology matrix-assisted laser desorption ionisa-tion time-of-flight (MALDI-TOF) based approaches currently used. Lipid modifications, such as the ones found on lipid A related to polymyxin resistance in Gram-negative pathogens (e.g. phosphoethanolamine, aminoarabinose), not only play a role in the detection of microorgan-isms by routine MALDI-TOF mass spectrometry but can also be used as a read-out of drug susceptibility. In this review, we will demonstrate that in combination with proteins, lipids are a game-changer in both the rapid detection of pathogens and the determination of their drug susceptibility using routine MALDI-TOF mass spectrometry systems.