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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Infection metallomics for critical care in the post-COVID era
Rutuja H Patil1,2, Dominika Luptáková1, Vladimír Havlíček1,2
1Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia.
Abstract:
Infection metallomics is a mass spectrometry (MS) platform we established based on the central concept that microbial metallophores are specific, sensitive, noninvasive, and promising biomarkers of invasive infectious diseases. Here we review the in vitro, in vivo, and clinical applications of metallophores from historical and functional perspectives, and identify under-studied and emerging application areas with high diagnostic potential for the post-COVID era. MS with isotope data filtering is fundamental to infection metallomics; it has been used to study the interplay between "frenemies" in hosts and to monitor the dynamic response of the microbiome to antibiotic and antimycotic therapies. During infection in critically ill patients, the hostile environment of the host's body activates secondary bacterial, mycobacterial, and fungal metabolism, leading to the production of metallophores that increase the pathogen's chance of survival in the host. MS can reveal the structures, stability, and threshold concentrations of these metal-containing microbial biomarkers of infection in humans and model organisms, and can discriminate invasive disease from benign colonization based on well-defined thresholds distinguishing proliferation from the colonization steady state.
Insights
Infection metallomics uses mass spectrometry to detect microbial metallophores, which are biomarkers for invasive infectious diseases. This approach aids in diagnosing infections and monitoring treatment responses.
Area of Science:
- Microbiology
- Analytical Chemistry
- Infectious Diseases
Background:
- Microbial metallophores are key molecules involved in pathogen survival and host-pathogen interactions.
- Invasive infectious diseases pose significant diagnostic challenges, especially in critically ill patients.
- Existing diagnostic methods may lack the specificity or sensitivity needed for early detection.
Purpose of the Study:
- To review the applications of metallophores as biomarkers for infectious diseases using mass spectrometry (MS).
- To explore the diagnostic potential of metallophores in the post-COVID era.
- To highlight emerging areas for metallophore-based diagnostics.
Main Methods:
- Infection metallomics platform utilizing mass spectrometry (MS) with isotope data filtering.
- In vitro, in vivo, and clinical studies of metallophores.
- Analysis of host-microbiome interactions and responses to therapies.
Main Results:
- Metallophores are produced by bacteria, mycobacteria, and fungi during infection, aiding pathogen survival.
- MS can identify metallophore structures, stability, and concentrations.
- Threshold concentrations can differentiate invasive infections from colonization.
Conclusions:
- Infection metallomics offers a sensitive and specific platform for diagnosing invasive infectious diseases.
- Metallophores hold significant potential as noninvasive biomarkers for various pathogens.
- Further research into under-studied metallophores can unlock new diagnostic applications.
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