Extracellular Enzymatic Activity of Candida Species Isolated from Patients with Head and Neck Cancer Undergoing Radiation Therapy and Its Correlation with Mucositis: A Cross-Sectional Study

Abstract

Introduction: The differences in enzymatic activity expressed by various Candida species determine their virulence and play a pivotal role in understanding the pathogenesis of candidiasis. Additionally, this knowledge aids in the development of new antifungal drugs that target these enzymes, thereby enhancing therapeutic approaches. Understanding the extracellular enzymatic activity of Candida species is crucial for the development of new anticandidial drugs targeting these enzymes. Aim: To determine the differences in enzymatic activity expressed by various Candida species isolated from patients with Head and Neck Cancer (HNC) undergoing Radiation Therapy (RT) and to correlate these differences with the severity of mucositis. Materials and Methods: This cross-sectional study evaluated the enzymatic activity of Candida species, including C. albicans and Non albicans Candida species (NAC), isolated from HNC patients undergoing RT at the radiation oncology department, Amala Institute of Medical Sciences, Thrissur, Kerala, India. A total of 276 patients were enrolled in the study over a four-year period (January 2019 to December 2022). Extracellular enzymatic activities such as proteinase, phospholipase, haemolysin, and esterase were detected using the plate method, as described previously. Mucositis was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Illinois, US). The Chi-square test was used to analyse the variables, and the unpaired t-test was used to compare enzymatic activity. Spearman’s rank correlation was used to identify any correlation between mucositis and extracellular enzymatic activity. Results: A total of 97 Candida strains (56 C. albicans and 41 NAC) were isolated. There was no statistically significant difference between C. albicans and NAC species causing infections in men and women (p-value=0.390), as well as in those with diabetes (p-value=0.127) and hypertension (p-value=0.979). Proteinase, haemolytic activity, and esterase production were detected in 88 (90.7%), 84 (86.6%), and 67 (69.0%) isolates, respectively, while phospholipase activity was shown by 18 (18.5%) isolates. There was no statistically significant difference between C. albicans and NAC species regarding the mean phospholipase, proteinase, haemolysin, and esterase activity (p-value>0.05). C. albicans exhibited high activity for all four enzymes, while a considerable percentage of NAC showed moderate activity. High phospholipase and proteinase activity in C. albicans showed a good correlation (r=0.148 and r=0.186, respectively) with mucositis. Conclusion: C. albicans showed high activity for all four enzymes, indicating its virulence. The majority of C. albicans strains exhibited proteinase activity, which is associated with the severity of mucosal infections. The phospholipase activity has the potential to play a role in the emergence of drug resistance and should be closely monitored.

Keywords

• candidiasis
• candida albicans
• drug resistance
• enzymes
• virulence