title: Fermentative 2-carbon metabolism produces carcinogenic levels of acetaldehyde in Candida albicans.
abstract: Acetaldehyde is a carcinogenic product of alcohol fermentation and metabolism in microbes associated with cancers of the upper digestive tract. In yeast acetaldehyde is a by-product of the pyruvate bypass that converts pyruvate into acetyl-Coenzyme A (CoA) during fermentation.
  
  
  OBJECTIVE
  (i) to determine the levels of acetaldehyde produced by Candida albicans in the presence of glucose in low oxygen tension in vitro; (ii) to analyse the expression levels of genes involved in the pyruvate-bypass and acetaldehyde production; and (iii) to analyse whether any correlations exist between acetaldehyde levels, alcohol dehydrogenase enzyme activity or expression of the genes involved in the pyruvate-bypass. Candida albicans strains were isolated from patients with oral squamous cell carcinoma (n = 5), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients with chronic oral candidosis (n = 5), and control patients (n = 5). The acetaldehyde and ethanol production by these isolates grown under low oxygen tension in the presence of glucose was determined, and the expression of alcohol dehydrogenase (ADH1 and ADH2), pyruvate decarboxylase (PDC11), aldehyde dehydrogenase (ALD6) and acetyl-CoA synthetase (ACS1 and ACS2) and Adh enzyme activity were analysed. The C. albicans isolates produced high levels of acetaldehyde from glucose under low oxygen tension. The acetaldehyde levels did not correlate with the expression of ADH1, ADH2 or PDC11 but correlated with the expression of down-stream genes ALD6 and ACS1. Significant differences in the gene expressions were measured between strains isolated from different patient groups. Under low oxygen tension ALD6 and ACS1, instead of ADH1 or ADH2, appear the most reliable indicators of candidal acetaldehyde production from glucose.
authors: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, FI-00014 Helsinki, Finland. emilia.marttila@helsinki.fi
authors: E
authors: E
authors: Marttila
authors: P
authors: P
authors: Bowyer
authors: D
authors: D
authors: Sanglard
authors: J
authors: J
authors: Uittamo
authors: P
authors: P
authors: Kaihovaara
authors: M
authors: M
authors: Salaspuro
authors: M
authors: M
authors: Richardson
authors: R
authors: R
authors: Rautemaa
mesh_terms: D000079:Acetaldehyde / Q000032:analysis / Q000378:metabolism*; D000106:Acetate-CoA Ligase / Q000235:genetics / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D002178:Candidiasis, Chronic Mucocutaneous / Q000382:microbiology; D002180:Candidiasis, Oral / Q000382:microbiology; D002244:Carbon / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000382:microbiology; D002326:Cariogenic Agents / Q000378:metabolism*; D000431:Ethanol / Q000032:analysis / Q000378:metabolism; D005285:Fermentation / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000382:microbiology; D010100:Oxygen / Q000737:chemistry; D016884:Polyendocrinopathies, Autoimmune / Q000382:microbiology; D011767:Pyruvate Decarboxylase / Q000235:genetics / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D002326:Cariogenic Agents; D005656:Fungal Proteins; D000431:Ethanol; D000105:Acetyl Coenzyme A; D002244:Carbon; D019289:Pyruvic Acid; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+); D011767:Pyruvate Decarboxylase; D000106:Acetate-CoA Ligase; D000079:Acetaldehyde; D005947:Glucose; D010100:Oxygen
keywords: APECED; Candida albicans; acetaldehyde; oral candidosis; oral carcinoma