title: 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.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. lee1983@hku.hk.
authors.forename: Kim-Chung
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. emily.wt@gmail.com.
authors.forename: Emily W T
authors.initials: EW
authors.lastname: Tam
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. lkc3309@gmail.com.
authors.forename: Ka-Ching
authors.initials: KC
authors.lastname: Lo
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. h0365593@graduate.hku.hk.
authors.forename: Alan K L
authors.initials: AK
authors.lastname: Tsang
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. candylaucy@gmail.com.
authors.forename: Candy C Y
authors.initials: CC
authors.lastname: Lau
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. kelvinto@hku.hk.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong. kelvinto@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong. kelvinto@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong. kelvinto@hku.hk.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: To
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. jfwchan@hku.hk.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong. jfwchan@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong. jfwchan@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong. jfwchan@hku.hk.
authors.forename: Jasper F W
authors.initials: JF
authors.lastname: Chan
authors.affiliation: Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong. ching-wanlam@pathology.hku.hk.
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. kyyuen@hku.hk.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong. kyyuen@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong. kyyuen@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong. kyyuen@hku.hk.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. skplau@hku.hk.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong. skplau@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong. skplau@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong. skplau@hku.hk.
authors.forename: Susanna K P
authors.initials: SK
authors.lastname: Lau
authors.affiliation: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong. pcywoo@hku.hk.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong. pcywoo@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong. pcywoo@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong. pcywoo@hku.hk.
authors.forename: Patrick C Y
authors.initials: PC
authors.lastname: Woo
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001228:Aspergillosis / Q000175:diagnosis* / Q000378:metabolism / Q000382:microbiology; D001230:Aspergillus / Q000472:pathogenicity*; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D010446:Peptide Fragments / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000893:Anti-Inflammatory Agents; D010446:Peptide Fragments
keywords: Aspergillus; biomarkers; metabolites; metabolomics; tetrapeptide