MALDI-TOF Mass Spectrometry Technology as a Tool for the Rapid Diagnosis of Antimicrobial Resistance in Bacteria

Abstract

Species identification by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a routine diagnostic process for infectious diseases in current clinical settings. The rapid, low-cost, and simple to conduct methodology is expanding its application in clinical microbiology laboratories to diagnose the antimicrobial resistance (AMR) in microorganisms. Primarily, antimicrobial susceptibility testing is able to be carried out either by comparing the area under curve of MALDI spectra of bacteria grown in media with antimicrobial drugs or by identifying the shift peaks of bacteria grown in media including 13C isotope with antimicrobial drugs. Secondly, the antimicrobial resistance is able to be determined through identifying (i) the antimicrobial-resistant clonal groups based on the fingerprints of the clone, (ii) the shift peak of the modified antimicrobial drug, which is inactivated by the resistance determinant, (iii) the shift peak of the modified antimicrobial target, (iv) the peak specific for the antimicrobial determinant, and (v) the biomarkers that are coproduced proteins with AMR determinants. This review aims to present the current usage of the MALDI-TOF MS technique for diagnosing antimicrobial resistance in bacteria, varied approaches for AMR diagnostics using the methodology, and the future applications of the methods for the accurate and rapid identification of AMR in infection-causing bacterial pathogens.

Combination of MALDI-TOF Mass Spectrometry and Machine Learning for Rapid Antimicrobial Resistance Screening: The Case of Campylobacter spp.

“…Mass spectra are routinely generated by MALDI-TOF MS and most of the time not exploited for additional analysis beyond the sole identification of microorganisms. Even if several reports highlighted successful applications of MALDI-TOF MS for detection of bacterial AMR, by the presence of specific biomarkers (Feucherolles et al, 2019a;Oviaño and Bou, 2019;Yoon and Jeong, 2021) identified by classical statistical methods, there is still a mine of information encrypted in the mass spectra. More recently, a growing number of reports combining MALDI-TOF mass spectrometry and ML have shown promising results for clinical big data problems, such as AMR screening (Weis et al, 2020a,b).…”

Recent Developments in Phenotypic and Molecular Diagnostic Methods for Antimicrobial Resistance Detection in Staphylococcus aureus: A Narrative Review

“…By using MALDI-TOF, several means exist to determine resistance or susceptibility to an antibiotic, e.g., the detection of proteins conferring resistance, the detection of a mass peak (biomarker) associated with resistance or antibiotic degradation. For reviews regarding the possibilities that MALDI-TOF offers in AST, please refer to these publications [ 59 , 60 , 61 , 62 , 63 ]. One notable advantage of the MALDI-TOF is that it could perform both identification and AST, simplifying the diagnostic workflow without the need to have separate methods.…”

Recent Advances in the Use of Molecular Methods for the Diagnosis of Bacterial Infections

“…Despite the progress, a current challenge of both platforms is the identification of pathogens directly from samples. In addition, another aspect that can significantly develop this technology is related to the ability to identify multiple bacteria in complex polymicrobial samples [86]. In this regard, several processing methods used for the preparation of different clinical samples, such as urine, cerebrospinal fluid, and blood, suitable for MALDI-TOF MS analysis have been proposed and are still in the process of standardization [86,87].…”

“…In addition, another aspect that can significantly develop this technology is related to the ability to identify multiple bacteria in complex polymicrobial samples [86]. In this regard, several processing methods used for the preparation of different clinical samples, such as urine, cerebrospinal fluid, and blood, suitable for MALDI-TOF MS analysis have been proposed and are still in the process of standardization [86,87]. Another critical challenge for MALDI-TOF MS in clinical microbiological diagnosis concerns the detection of antibiotic resistance [88] and the activation of drug efflux pumps [1].…”