Present and future perspectives on mass spectrometry for clinical microbiology

In the last decade, MALDI-TOF Mass Spectrometry (MALDI-TOF MS) has been introduced and broadly accepted by clinical laboratory laboratories throughout the world as a powerful and efficient tool for rapid microbial identification. During the MALDI-TOF MS process, microbes are identified using either intact cells or cell extracts. The process is rapid, sensitive, and economical in terms of both labor and costs involved. Whilst MALDI-TOF MS is currently the gold-standard, it suffers from several shortcomings such as lack of direct information on antibiotic resistance, poor depth of analysis and insufficient discriminatory power for the distinction of closely related bacterial species or for reliably sub-differentiating isolates to the level of clones or strains. Thus, new approaches targeting proteins and allowing a better characterization of bacterial strains are strongly needed, if possible, on a very short time scale after sample collection in the hospital. Bottom-up proteomics (BUP) is a nice alternative to MALDI-TOF MS, offering the possibility for in-depth proteome analysis. Top-down proteomics (TDP) provides the highest molecular precision in proteomics, allowing the characterization of proteins at the proteoform level. A number of studies have already demonstrated the potential of these techniques in clinical microbiology. In this review, we will discuss the current state-of-the-art of MALDI-TOF MS for the rapid microbial identification and detection of resistance to antibiotics and describe emerging approaches, including bottom-up and top-down proteomics as well as ambient MS technologies.