Studies on pathogenic mechanisms of non-albicans Candida derived from oral cancer patients

Ali Nawaz

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Mouth is a primary source of infections and Candida infections are associated with mortality. Oral Candida infections can be life threatening in medically compromised patients, particularly non-albicans Candida (NAC) strains are virulent. Candida associated diseases are mostly superficial, however as the disease persists it may cause systemic infections particularly in immunocompromised patients. The present study aims were to investigate differences in proteolytic activity of Candida strains and examine the prevalence of Candida strains in oral cancer patients of the Helsinki University Hospital. Clinical and reference yeast samples from our laboratory were also used for further analyses. One hundred patients with squamous cell carcinoma of oral cavity were recruited to the study. Paraffin wax stimulated saliva samples were collected and cultivated on CHROMagar Candida medium. The API ID 32C yeast identification kit and Bichro-Dubli Fumouze latex agglutination test were used for Candida species identification. Candida strains were grown in yeast peptone glucose and Candida proteinase activity was analyzed using MDPF-gelatin zymography, fluorometric assays and degradation assays were performed using claudin-4 (CLDN-4) and human plasma fibronectin (pFn). The effect of pH and fermented lingonberry juice (FLJ) on intracellular protein expression of C. glabrata was assessed using the 2D-DIGE method. The levels of IL-1β, IL-10, and TNF-α were measured using ELISA of saliva samples collected from elderly residents of Helsinki. These studies showed that Candida albicans (C. albicans) was the most common species in oral cavity of oral carcinoma patients. Differences existed in the proteolytic activity of non-albicans Candida (NAC) and C. albicans strains. The Candida strains degraded fibronectin and CLDN-4 and the degradation ability varied among the strains. The degradation of tight junction and extracellular proteins may lead to loss of epithelial tight junction integrity and predispose to Candida invasion or oral cancer development particularly in chronic mucocutaneous candidosis C. tropicalis showed higher proteolytic activity compared with the other strains. Higher proteolytic activity may thus influence and partly explain the virulence of the NAC strains. FLJ caused down regulation of C. glabrata T-1639 adenylate kinase expression leading to diminished adenosine diphosphate (ADP) availability involved in the oxidative phosphorylation. It causes downregulation of glyceraldehyde-3-phosphate dehydrogenase 2 (GADPH-2) in C. glabrata. GADPH plays a role in the carbohydrate processing and one of the early steps in glycolysis. Hence FLJ caused reduction of energy supplies and inhibited yeast cell growth. These factors may be involved in the prevention of pathological biofilm accumulation. The results showed a significant increase in IL-1β levels in subjects with NAC compared to Candida-negative saliva samples. NAC may play a role in tissue inflammatory response by inducing cytokine response. The preoperative analysis of Candida infections may indeed play a role in early diagnosis together with respective analyses of the risks in population. Clarifying the molecular mechanisms may provide new means for understanding the role of yeasts in the development of oral cancer.
Original languageEnglish
Supervisors/Advisors
  • Meurman, Jukka, Supervisor
  • Pärnänen, Pirjo Annikki, Supervisor
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-8061-2
Electronic ISBNs978-951-51-8062-9
Publication statusPublished - 2022
MoE publication typeG5 Doctoral dissertation (article)

Bibliographical note

M1 - 53 s. + liitteet

Fields of Science

  • Mouth Neoplasms
  • +mortality
  • Squamous Cell Carcinoma of Head and Neck
  • Yeasts
  • Candidiasis, Oral
  • Candida albicans
  • Candida tropicalis
  • Candida glabrata
  • +enzymology
  • Biofilms
  • Saliva
  • Cytokines
  • Fibronectins
  • Claudin-4
  • Vaccinium vitis-idaea
  • Fermented Beverages
  • Collagen
  • Extracellular Matrix
  • Proteolysis
  • 313 Dentistry

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