Surfomics: shaving live organisms for a fast proteomic identification of surface proteins

Surface proteins play a critical role in the interaction between cells and their environment, as they take part in processes like signaling, adhesion, transport, etc. In pathogenic microorganisms, they can also participate in virulence or cytotoxicity. As these proteins have the highest chances to be recognized by the immune system, they are often the targets for the discovery of new vaccines. In addition, they can serve for the development of serological-based tools to diagnose infectious diseases. First-generation proteomic strategies for the identification of surface proteins rely on the biochemical fractionation and/or enrichment of this group of molecules or organelles containing them. However, in the last years, a novel second-generation approach has been developed, consisting of the digestion of live, intact cells with proteases, so that surface-exposed moieties (i.e. the "surfome" of a cell) are "shaved" and analyzed by LC/MS/MS. Here we review such a strategy, firstly set up and developed in Gram-positive bacteria, and further applied to Gram-negative bacteria, unicellular fungi, and also pluricellular organisms. We also discuss the advantages and inconvenients of the approach, and the still unresolved question about the intriguing presence of proteins predicted as cytoplasmic in the surfomes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.