Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

Abstract

Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.

A 10-year study reveals clinical and laboratory evidence for the ‘semi-invasive’ properties of chronic pulmonary aspergillosis

“…Although a number of novel diagnostic tests have been developed for pulmonary aspergillosis, serum galactomannan antigen and anti- Aspergillus antibody remain the most widely used non-invasive tests in most laboratories. 10 , 11 , 12 , 13 , 14 , 15 We observed several important phenomena when comparing the performance of serum galactomannan antigen, serum anti- Aspergillus antibody, and culture of respiratory tract specimens among the three groups. Firstly, an increasing trend in the seropositive rate of galactomannan antigen from PA (24.1%) to CPA (35.7%) to IPA (54.9%) and an opposite trend for anti- Aspergillus antibody (PA, 71.0% CPA, 45.8% IPA, 7.1%) were noted ( Table 2 ).…”

Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei

“…Aspergitides are NRP-derived tetrapeptides which are potentially anti-inflammatory (Lee et al 2015 ). These hydrophobic tetrapeptides have some similarity with fungisporins and nidulanins which appear to be generally present in Aspergillus and Penicillium species (Ali et al 2014 ; Klitgaard et al 2015 ; Hautbergue et al 2017 ).…”

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

“…The metabolic profiles between such systems can then be compared, thus allowing the identification of specific metabolite markers. The technique has been used to characterize various infectious diseases or pathogens [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. By exploring the metabolomes of culture supernatant, we have identified specific biomarkers that are produced by a unique thiamine degradation pathway in B. pseudomallei [ 32 ].…”