We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Invasive candidiasis (IC) and invasive aspergillosis (IA) are major life-threatening nosocomial invasive fungal infections (IFIs) (1-3). Although less prevalent, mucormycosis (MM) is an emerging problem. Progress in antifungal therapy has not significantly reduced the high rates of morbidity and mortality associated with IFIs, particularly in intensive care units (ICUs) and oncohematology units (4-6), due to difficulties in obtaining an early diagnosis, an important condition for a favorable outcome (7). Difficulties in the biological detection of IFIs are related to the low yield of culture-based methods (8); blood cultures are positive in only ϳ50% of episodes of IC and in anecdotic cases of IA. To fill this gap, methods have been developed for the detection of fungal molecules in sera from patients (9-11). These methods include the detection of fungal DNA in body fluids and tissues, for which no consensual recommendations have been produced due to the lack of standardization. In contrast, there is extensive literature on the diagnostic value of fungal polysaccharide detection, including (1,3)--D-glucan (BDG) (12), present in Candida and Aspergillus cell walls, and mannan (Mnn) or galactomannan (GM), found in Candida and Aspergillus, respectively. Each of these assays, which present different compromises between sensitivity and specificity, are currently widely used, although there is a lack of consensus about therapeutic decisions based on the results of these tests in the complex setting of IC and IA (13-15). For MM, no serological test is currently of diagnostic help.In a previous report, we described the presence of a specific m/z 365 matrix-assisted laser desorption ionization (MALDI) mass spectrometry (
The diagnosis of systemic Candida infections is a recognized challenge. We developed a mass spectrometry strategy to detect signals from Candida molecules in patients' sera. Pre-analytical procedures were designed to extract oligosaccharides from serum. A peak m/z of at 365 was specifically revealed in sera from patients with candidaemia with regard to healthy controls. This biomarker was identified as a disaccharide, its presence did not correlate with mannanaemia or glucanaemia. Mouse models of Candida albicans colonization and infection showed that the signal was specifically associated with tissue invasion, suggesting that clinical evaluation of its usefulness in discriminating colonized and infected patients would be worthwhile.
Despite impressive progress made over the past 20 years in our understanding of mycolylarabinogalactan-peptidoglycan (mAGP) biogenesis, the mechanisms by which the tubercle bacillus Mycobacterium tuberculosis adapts its cell wall structure and composition to various environmental conditions, especially during infection, remain poorly understood. Being the central portion of the mAGP complex, arabinogalactan (AG) is believed to be the constituent of the mycobacterial cell envelope that undergoes the least structural changes, but no reports exist supporting this assumption. Herein, using recombinantly expressed mycobacterial protein, bioinformatics analyses, and kinetic and biochemical assays, we demonstrate that the AG can be remodeled by a mycobacterial endogenous enzyme. In particular, we found that the mycobacterial GlfH1 (Rv3096) protein exhibits exo-β-d-galactofuranose hydrolase activity and is capable of hydrolyzing the galactan chain of AG by recurrent cleavage of the terminal β-(1,5) and β-(1,6)-Galf linkages. The characterization of this galactosidase represents a first step toward understanding the remodeling of mycobacterial AG.
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