Applications of Proteomics to Clinical Microbiology

Abstract

The most successful clinical application of proteomics to date is MALDI-TOF MS based bacterial identification. As compared with the conventional methods, the MS-based method is more quick and simple; indeed, there has been a revolutionary shift in clinical diagnostic microbiology.

A small portion of a cultured bacterial colony is directly subjected to MALDI-TOF MS. The final mass spectral signature is composed of peaks originating from bacterial proteins including mainly ribosomal proteins. The spectral profiles are compared with a library of known spectra and a result is generated within 10 min instead of almost one day when conducted by the traditional methods.

The rate of successful identification at the species levels, however, is still not 100% for various reasons such as incomplete databases. We have found that in-house refinement of commercial database by incorporating MS spectra of clinical isolates obtained locally can significantly improve the identification rate. Also, for some pathogens, extensive pretreatment of the samples is mandatory to obtain appropriate proteomic profiles. Progress has been made for direct analysis of bacteria in urine, cerebrospinal fluid (CSF), and blood. Beyond identification of bacteria, MS is increasingly used for detection of antibiotic resistance. For this purpose, LC/MS/MS may play roles as well.

To meet with rapid progress in clinical applications of MS, the Japanese Society for Biomedical Mass Spectrometry has started to certify medical mass spectrometrist since 2013. As of June 2017, a total of 298 have been certified.