{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:36:03Z","timestamp":1771259763309,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013Glu\u2013Leu\u2013Glu, 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\u2013Glu\u2013Leu\u2013Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.<\/jats:p>","DOI":"10.3390\/ijms160613850","type":"journal-article","created":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T11:19:34Z","timestamp":1434539974000},"page":"13850-13867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species"],"prefix":"10.3390","volume":"16","author":[{"given":"Kim-Chung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ka-Ching","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candy","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelvin","family":"To","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong,  Pokfulam, Hong Kong"},{"name":"Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6336-6657","authenticated-orcid":false,"given":"Jasper","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong,  Pokfulam, Hong Kong"},{"name":"Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Wan","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwok-Yung","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong,  Pokfulam, Hong Kong"},{"name":"Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1383-7374","authenticated-orcid":false,"given":"Susanna","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong,  Pokfulam, Hong Kong"},{"name":"Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong,  Pokfulam, Hong Kong"},{"name":"Research Centre of Infection and Immunology, The University of Hong Kong, Pokfulam, Hong Kong"},{"name":"Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1128\/CMR.12.2.310","article-title":"Aspergillus fumigatus and aspergillosis","volume":"12","author":"Latge","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1128\/JCM.39.11.3830-3837.2001","article-title":"Characterization of AFMP1: A novel target for serodiagnosis of aspergillosis","volume":"39","author":"Yuen","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1128\/JCM.40.11.4382-4387.2002","article-title":"Detection of cell wall galactomannoprotein Afmp1p in culture supernatants of aspergillus fumigatus and in sera of aspergillosis patients","volume":"40","author":"Woo","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1128\/JCM.41.2.845-850.2003","article-title":"Aflmp1 encodes an antigenic cell wall protein in Aspergillus flavus","volume":"41","author":"Woo","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1128\/JCM.42.5.2287-2291.2004","article-title":"Afmp2 encodes a novel immunogenic protein of the antigenic mannoprotein superfamily in Aspergillus fumigatus","volume":"42","author":"Chong","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1086\/514492","article-title":"Stage-specific manifestation of mold infections in bone marrow transplant recipients: Risk factors and clinical significance of positive concentrated smears","volume":"25","author":"Yuen","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1128\/JCM.40.6.2041-2045.2002","article-title":"Detection of antibodies specific to an antigenic cell wall galactomannoprotein for serodiagnosis of Aspergillus fumigatus aspergillosis","volume":"40","author":"Chan","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"459405","DOI":"10.1155\/2013\/459405","article-title":"Laboratory diagnosis of invasive aspergillosis: From diagnosis to prediction of outcome","volume":"2013","author":"Barton","year":"2013","journal-title":"Scientifica"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jhin.2011.01.020","article-title":"Environmental and clinical epidemiology of Aspergillus terreus: Data from a prospective surveillance study","volume":"78","author":"Ruping","year":"2011","journal-title":"J. Hosp. Infect."},{"key":"ref_10","first-page":"2655","article-title":"An overview of tuberculosis treatments and diagnostics. What role could metabolomics play","volume":"11","author":"Olivier","year":"2011","journal-title":"J. Cell Tissue Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.mimet.2012.01.012","article-title":"A metabolomics approach to characterise and identify various mycobacterium species","volume":"88","author":"Olivier","year":"2012","journal-title":"J. Microbiol. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1007\/s11306-012-0424-6","article-title":"A metabolomics investigation of a hyper-and hypo-virulent phenotype of beijing lineage M. tuberculosis","volume":"8","author":"Koekemoer","year":"2012","journal-title":"Metabolomics"},{"key":"ref_13","first-page":"2673","article-title":"Improved disease characterisation and diagnostics using metabolomics: A review","volume":"11","author":"Schoeman","year":"2011","journal-title":"J. Cell Tissue Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7562","DOI":"10.1021\/ac800954c","article-title":"Analysis of metabolomic data using support vector machines","volume":"80","author":"Mahadevan","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1155\/2004\/530647","article-title":"The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis","volume":"19","author":"Van","year":"2003","journal-title":"Dis. Markers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4752","DOI":"10.1039\/c1an15590c","article-title":"Development of an integrated metabolomic profiling approach for infectious diseases research","volume":"136","author":"Lv","year":"2011","journal-title":"Analyst"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1128\/JCM.03258-13","article-title":"Misidentification of Aspergillus nomius and Aspergillus tamarii as Aspergillus flavus: Characterization by internal transcribed spacer, beta-tubulin, and calmodulin gene sequencing, metabolic fingerprinting, and matrix-assisted laser desorption ionization-time of flight mass spectrometry","volume":"52","author":"Tam","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1128\/JCM.02845-12","article-title":"Characterization of a tsukamurella pseudo-outbreak by phenotypic tests, 16s rRNA sequencing, pulsed-field gel electrophoresis, and metabolic footprinting","volume":"51","author":"To","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1871","DOI":"10.1371\/journal.pntd.0001871","article-title":"First discovery of two polyketide synthase genes for mitorubrinic acid and mitorubrinol yellow pigment biosynthesis and implications in virulence of Penicillium marneffei","volume":"6","author":"Woo","year":"2012","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1038\/emi.2015.6","article-title":"Identification of specific metabolites in culture supernatant of mycobacterium tuberculosis using metabolomics: Exploration of potential biomarkers","volume":"4","author":"Lau","year":"2015","journal-title":"Emerg. Microbes Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.fgb.2014.04.011","article-title":"Characterization of the biosynthetic gene cluster for the ribosomally synthesized cyclic peptide ustiloxin B in Aspergillus flavus","volume":"68","author":"Umemura","year":"2014","journal-title":"Fungal Genet. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1021\/np300897v","article-title":"Asperterrestide A, a cytotoxic cyclic tetrapeptide from the marine-derived fungus Aspergillus terreus SCSGAF0162","volume":"76","author":"He","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/2193-1801-1-58","article-title":"COX-2 structural analysis and docking studies with gallic acid structural analogues","volume":"1","author":"Amaravani","year":"2012","journal-title":"SpringerPlus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0021-9673(03)00490-4","article-title":"Fungal metabolite screening: Database of 474 mycotoxins and fungal metabolites for dereplication by standardised liquid chromatography\u2013UV\u2013mass spectrometry methodology","volume":"1002","author":"Nielsen","year":"2003","journal-title":"J. Chromatogr. A"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Versalovic, J., Carroll, K., Funke, G., Jorgensen, J., Landry, M., and Warnock, D. (2011). Manual of Clinical Microbiology, ASM Press.","DOI":"10.1128\/9781555816728"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.diagmicrobio.2012.06.014","article-title":"Phaeoacremonium parasiticum invasive infections and airway colonization characterized by agar block smear and its and beta-tubulin gene sequencing","volume":"74","author":"To","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.diagmicrobio.2009.10.009","article-title":"Lichtheimia hongkongensis sp. Nov., a novel lichtheimia spp. associated with rhinocerebral, gastrointestinal, and cutaneous mucormycosis","volume":"66","author":"Woo","year":"2010","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00644","DOI":"10.1128\/genomeA.00644-14","article-title":"Complete mitochondrial genome sequence of lichtheimia ramosa (syn. Lichtheimia hongkongensis)","volume":"2","author":"Leung","year":"2014","journal-title":"Genome Announc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1128\/JCM.00619-07","article-title":"Mp1 homologue-based multilocus sequence system for typing the pathogenic fungus Penicillium marneffei: A novel approach using lineage-specific genes","volume":"45","author":"Woo","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6728","DOI":"10.1038\/srep06728","article-title":"The biosynthetic pathway for a thousand-year-old natural food colorant and citrinin in Penicillium marneffei","volume":"4","author":"Woo","year":"2014","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/6\/13850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:48:00Z","timestamp":1760215680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/6\/13850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,17]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["ijms160613850"],"URL":"https:\/\/doi.org\/10.3390\/ijms160613850","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,17]]}}}