Peptide profiling by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry of the Lasiodora parahybana tarantula venom gland.

In order to establish a venom fingerprint and a peptide profile of the Lasiodora parahybana tarantula venom gland, we used conventional methods such as reversed phase liquid chromatography coupled to an electrospray-ionisation hybrid quadrupole time of flight mass spectrometer (LC/ESI-QqTOFMS), matrix-assisted laser desorption/ionization time-of-flight-MS (MALDI-TOFMS) and direct study of L. parahybana venom by nanospray-ionization QqTOFMS (nanoESI-QqTOFMS) and a new technology for the direct analysis of fresh tissues using MALDI-TOFMS. The analysis of the crude venom allowed the characterization of specific juvenile and adult biomarkers. In situ MALDI analysis of L. parahybana venom gland sections revealed different peptide expression levels all along the gland and non-processed peptide precursors, demonstrating the power of the method for the dynamic investigation of peptide evolution in the venom gland of spiders.     

Alkaloid profiling in crude and processed Strychnos nux-vomica seeds by matrix-assisted laser desorption/ionization-time of flight mass spectrometry

Direct analysis of alkaloids in the tissues of crude and processed Strychnos nux-vomica seeds by MALDI-TOFMS was described. The alkaloid profiles of the herb drugs were obtained without the need of complicated sample preparation to avoid potential damage or change of the active components. Seed tissues that were optimally sliced to a thickness of 10-20 microm from the crude and processed Strychnos nux-vomica seeds as well as various parts of tissue such as endosperm and epidermis were analyzed on MALDI target plate after the matrix was directly applied onto the tissue surface. The obtained alkaloid profiles provided valuable information for the differentiation of crude and processed Strychnos nux-vomica seeds and for the explanation of the significantly different toxicity. Experimental results indicated that the direct MALDI-TOFMS analysis allowed rapid screening of the alkaloid components in Strychnos nux-vomica seeds.     

An Alzheimer's disease-specific β-amyloid fragment signature in cerebrospinal fluid

Pathogenic events in Alzheimer's disease (AD) involve an imbalance between the production and clearance of the neurotoxic β-amyloid peptide (Aβ), especially the 42 amino acid peptide Aβ1–42. While much is known about the production of Aβ1–42, many questions remain about how the peptide is degraded. To investigate the degradation pattern, we developed a method based on immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry that determines the Aβ degradation fragment pattern in cerebrospinal fluid (CSF). We found in total 18 C-terminally and 2 N-terminally truncated Aβ peptides and preliminary data indicated that there were differences in the detected Aβ relative abundance pattern between AD and healthy controls. Here, we provide direct evidence that an Aβ fragment signature consisting of Aβ1–16, Aβ1–33, Aβ1–39, and Aβ1–42 in CSF distinguishes sporadic AD patients from non-demented controls with an overall accuracy of 86%.     

MALDI-TOFMS-oriented early definitive therapy improves the optimal use of antibiotics for Enterococcus spp. bloodstream infection

Enterococci is one of a major cause of bloodstream infection (BSI). Because of its intrinsic drug-resistant nature, empiric antibiotic treatment tends to be inappropriate. We conducted a single-center retrospective cohort study to evaluate the impact of Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOFMS) on the improvement of early antibiotic treatment for enterococcal infection. We also investigated the 28-day mortality, length of hospitalization and duration of antibiotic treatment for enterococcal bacteremia. A total of 173 BSI episodes (172 patients) between June 2012 and June 2019 were enrolled. Patients were divided into 2 groups before (n = 82) and after (n = 91) the implementation of MALDI-TOFMS (Control group and MALDI-TOF group, respectively). Almost an equal number of Enterococcus faecalis and Enterococcus faecium cases were identified in each group (51.2% and 48.8%, and 47.3% and 52.7% in each group). By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly improved (median 3 vs 1 days, p < 0.001). The 28-day mortality (29.3% vs 26.4%, p = 0.63) and length of hospitalization (median 16 vs 19 days, p = 0.58) were not significantly different. The duration of antibiotic treatment did not significantly differ between the two groups (median 11 vs 11 days, p = 0.78), but the duration was often shorter in older patients (>74 years old) in MALDI-TOF group, excluding those in the terminal phase of malignancy. By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly shortened. Although associated outcomes did not significantly differ, the duration of antibiotic treatment may be shortened.