Infection metallomics for critical care in the post‐COVID era

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.

Siderophore-Based Noninvasive Differentiation of Aspergillus fumigatus Colonization and Invasion in Pulmonary Aspergillosis

“…Applying our infection metallomics strategy ( 24 ), the characteristic A. fumigatus siderophores identified from the in vitro study (Movie S1) were screened for in all patient urine and serum samples. Fc, TafC, TafB, and Gtx were the main secondary metabolites detected in IPA patients ( Tables 1 and 2 ; Table S2).…”

“…4 ). Thus, their appearance in a host, defined by the limit of detection (LOD) of the infection metallomics approach ( 24 ), provides early, sensitive, and specific noninvasive detection of A. fumigatus -induced IPA in humans.…”

“…The use of urine and serum samples in the observational, noninterventional study was approved by the Ethics Committee for Clinical Trials of the Institute of Public Health (EC-02/18) and the University Hospital Ostrava (448/2018), and informed-consent documents were obtained from study participants. Analyses of patient urine and serum samples were performed using the LC-MS-based infection metallomics approach ( 24 ). Throughout the study, we strove to adhere to the good clinical practice guidelines outlined by the Declaration of Helsinki (2013).…”

“…Here, we demonstrate the potential utility of infection metallomics ( 24 ) for the clinical diagnosis of IPA based on the noninvasive detection in urine of the intra- and extracellular siderophore TafC, its hydrolytic product triacetylfusarinine B (TafB) ( 11 ), Fc, and a secondary metabolite, Gtx. We present clear links between germination or infection phase-dependent siderophore production and observations in critically ill patients.…”

Cyclic heptapeptides with metal binding properties isolated from the fungus Cadophora malorum from Antarctic soil

“…Metallomics integrates multidisciplinary research for the study of the relationships between bio-metals to bio-function. One of the fields of increasing interest in this area is the study of the metal coordination capability of metabolites, which may account for many biological activities such as metal hijacking, resistance to reactive oxygen species, production of sexual spores in microorganisms [ 10 ].…”