Recent Advances and Ongoing Challenges in the Diagnosis of Microbial Infections by MALDI-TOF Mass Spectrometry

Abstract

Timeliness and accuracy in the diagnosis of microbial infections are associated with decreased mortality and reduced length of hospitalization, especially for severe, life-threatening infections. A rapid diagnosis also allows for early streamlining of empirical antimicrobial therapies, thus contributing to limit the emergence and spread of antimicrobial resistance. The introduction of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) for routine identification of microbial pathogens has profoundly influenced microbiological diagnostics, and is progressively replacing biochemical identification methods. Compared to currently used identification methods, MALDI-TOF MS has the advantage of identifying bacteria and yeasts directly from colonies grown on culture plates for primary isolation in a few minutes and with considerable material and labor savings. The reliability and accuracy of MALDI-TOF MS in identification of clinically relevant bacteria and yeasts has been demonstrated by several studies showing that the performance of MALDI-TOF MS is comparable or superior to phenotypic methods currently in use in clinical microbiology laboratories, and can be further improved by database updates and analysis software upgrades. Besides microbial identification from isolated colonies, new perspectives are being explored for MALDI-TOF MS, such as identification of pathogens directly from positive blood cultures, sub-species typing, and detection of drug resistance determinants. In this review, we summarize the state of the art in routine identification of microbial pathogens by MALDI-TOF MS, and highlight recent advancements of this technology in special applications, such as strain typing, assessment of drug susceptibility, and detection of virulence factors.

Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping

“…Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) MS-based microbial species identification has emerged as an alternative to traditional phenotypic-or genotypic-based methods (7)(8)(9)(10). Demonstrating benefits, such as reliable species-level resolution, in most cases, ease-of-use and speed of processing samples, as well as low cost per analysis, MALDI-TOF MS identification is now used in clinics world-wide.…”

Global guidelines and initiatives from the European Confederation of Medical Mycology to improve patient care and research worldwide: New leadership is about working together

“…[21][22][23] Finally, the increasing availability of new nucleic acid amplification assays, blood culture detection systems, lateral flow devices, as well as matrix-assisted laser desorption time of flight (MALDI-TOF) mass spectrometry for detection of medically important fungi and laboratory diagnosis of invasive mycoses warrants guidance in their use in clinical practice. [24][25][26][27] To respond adequately to these tasks, international societies of medical mycology have joined forces with a goal of improving diagnosis, treatment, prevention, and survival of persons with invasive fungal infections worldwide. Here, we highlight some of the most important outreach initiatives, spearheaded by the European Confederation of | 887…”

“…Moreover, new antifungal agents have recently become available or are being developed that warrant up‐to‐date guidance on optimal treatment of IFDs . Finally, the increasing availability of new nucleic acid amplification assays, blood culture detection systems, lateral flow devices, as well as matrix‐assisted laser desorption time of flight (MALDI‐TOF) mass spectrometry for detection of medically important fungi and laboratory diagnosis of invasive mycoses warrants guidance in their use in clinical practice …”

MALDI-TOF Mass Spectrometry and Specific Biomarkers: Potential New Key for Swift Identification of Antimicrobial Resistance in Foodborne Pathogens

“…Since the introduction of mass spectrometry in the field of microbiology, the speed of pathogen identification has tremendously increased, thereby improving antimicrobial therapy, infection prevention and leading to a major impact in public health and epidemiology [42]. Today, direct antimicrobial resistance detection in the acquired mass spectra is one of the most suggested and asked about applications in specialized reviews [43][44][45][46][47]. Four main uses have been successfully tested: (1) the detection and expression of antibiotic resistance mechanisms (e.g., β-Lactamase, rRNA methyl-transferase activity), (2) specific mass peak profiles within spectra, (3) the detection of stable isotope-labeled biomarkers and (4) the estimation of the effect of antibiotics on microorganism growth.…”