Pathogen Identification Direct From Polymicrobial Specimens Using Membrane Glycolipids

Fondrie, William E.; Liang, Tao; Oyler, Benjamin L.; Leung, Lisa M.; Ernst, Robert K.; Strickland, Dudley K.

doi:10.1038/s41598-018-33681-8

Cited by 18 publications

(24 citation statements)

References 36 publications

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“…For instance, this methodology has been shown to be useful for the detection of protein toxins, such as staphylococcal enterotoxin B, botulinum neurotoxins, Clostridium perfringens epsilon toxin, and Shiga toxin, which can be potential bioterrorism agents when they are delivered via an aerosol route [ 77 , 78 ]. In addition, the identification of multiple bacteria in complex polymicrobial mixtures [ 79 ] is another aspect we expect to be developed through this methodology.…”

Section: Future Aspectsmentioning

confidence: 99%

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

Yoon

Jeong

2021

Antibiotics

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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.

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Section: Future Aspectsmentioning

confidence: 99%

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

Yoon

Jeong

2021

Antibiotics

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“…In addition, they employed the existing MALDI Biotyper software to construct a glycolipid library containing 50 microbial entries ( Leung et al., 2017 ). This dataset was used in the subsequent machine learning study to identify A. baumannii and K. pneumoniae from polymicrobial mixtures, such as urinary tract infection specimens ( Fondrie et al., 2018 ).…”

Section: Lipid-profiling By Maldi-tof For Microbial Identificationmentioning

confidence: 99%

Detection of Species-Specific Lipids by Routine MALDI TOF Mass Spectrometry to Unlock the Challenges of Microbial Identification and Antimicrobial Susceptibility Testing

Solntceva

Kostrzewa

Larrouy-Maumus

2021

Front. Cell. Infect. Microbiol.

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MALDI-TOF mass spectrometry has revolutionized clinical microbiology diagnostics by delivering accurate, fast, and reliable identification of microorganisms. It is conventionally based on the detection of intracellular molecules, mainly ribosomal proteins, for identification at the species-level and/or genus-level. Nevertheless, for some microorganisms (e.g., for mycobacteria) extensive protocols are necessary in order to extract intracellular proteins, and in some cases a protein-based approach cannot provide sufficient evidence to accurately identify the microorganisms within the same genus (e.g., Shigella sp. vs E. coli and the species of the M. tuberculosis complex). Consequently lipids, along with proteins are also molecules of interest. Lipids are ubiquitous, but their structural diversity delivers complementary information to the conventional protein-based clinical microbiology matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) based approaches currently used. Lipid modifications, such as the ones found on lipid A related to polymyxin resistance in Gram-negative pathogens (e.g., phosphoethanolamine and aminoarabinose), not only play a role in the detection of microorganisms by routine MALDI-TOF mass spectrometry but can also be used as a read-out of drug susceptibility. In this review, we will demonstrate that in combination with proteins, lipids are a game-changer in both the rapid detection of pathogens and the determination of their drug susceptibility using routine MALDI-TOF mass spectrometry systems.

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“…Native lipid A peak(s) (m/z) Modified lipid A peak(s) (m/z) Lipid A modification effort has already been made towards this in a study showing that machine learning algorithms and MALDI-TOF mass spectrometry can be used to detect colistin-resistant Acinetobacter and Klebsiella spp. in complex polymicrobial mixtures [29]. .…”

Section: Organismmentioning

confidence: 99%

The clue is in the lipid A: Rapid detection of colistin resistance

et al. 2020

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Matrix-assisted laser desorption/ionization-time of flight mass spectrometry is an emerging technology for the detection of antimicrobial resistance Antimicrobial resistance (AMR) is one of the biggest public health concerns of our time [1]. Currently, resistance has been reported for almost all available antibiotics, from first-line to last-resort drugs [2]. AMR restricts treatment options, leads to increased morbidity and mortality of hospitalized patients and imposes a substantial financial burden on healthcare systems worldwide [3]. The limited pipeline of new antimicrobials and the continuous emergence of multidrug-resistant (MDR) organisms needs to be countered by novel antibacterial strategies coupled with rapid diagnostics to detect resistance, particularly in the case of broad-acting agents such as β-lactams and polymyxins. Traditionally, antimicrobial susceptibility testing is performed using culture-based methods, like minimum inhibitory concentration (MIC) determination assays, a lengthy process that is prone to misleading results, for example, in the case of clinical isolates that produce large amounts of capsule or biofilm. By contrast, polymerase-chain-reaction (PCR)-based tests like multiplex PCR allow the rapid identification of specific resistance factors but cannot predict susceptibility and are entirely insensitive to uncharacterized mechanisms of resistance. At the same time, despite the extensive progress of genotypic sequence-based approaches, such as long-read nanopore sequencing, these cannot yet be used as first-line diagnostics in part because genotype-to-phenotype predictions remain challenging [4,5]. With matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry being used routinely for bacterial identification in clinical settings, a range of MAL-DI-TOF-based diagnostics for the rapid detection of AMR are starting to be implemented [6,7]. More specifically, it is possible to discriminate some lineages of methicillin-resistant Staphylococcus aureus, identify certain strains of enterobacteria carrying plasmid-encoded βlactamases from the Klebsiella pneumoniae carbapenemase (KPC) family of enzymes, and detect Bacteroides fragilis strains that are resistant to β-lactams at the same time as performing bacterial identification. Alongside these identification-based approaches, efforts to identify both aminoglycoside and quinolone resistance using MALDI-TOF mass spectrometry have also been made. As resistance to these agents can arise through enzymatic modification of the antibiotic, this modification can be directly detected following incubation of the drug of interest with resistant bacteria [8,9]. Nonetheless, probably the most successful application of MAL-DI-TOF mass spectrometry for AMR detection to date has been functional screening for βlactamase activity. Bacteria are mixed with a β-lactam compound, and an increase in the

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Pathogen Identification Direct From Polymicrobial Specimens Using Membrane Glycolipids

Cited by 18 publications

References 36 publications

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

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

Detection of Species-Specific Lipids by Routine MALDI TOF Mass Spectrometry to Unlock the Challenges of Microbial Identification and Antimicrobial Susceptibility Testing

The clue is in the lipid A: Rapid detection of colistin resistance

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