Assessing pH‐dependent activities of virulence factors secreted by Candida albicans

Abstract

Candida albicans is an opportunistic pathogen that can thrive under adverse conditions including suboptimal pH, nutrient scarcity, and low levels of oxygen. Its pathogenicity is associated with the production of virulence factors such as extracellular hydrolytic enzymes and toxins. This study was aimed at determining the effect of external pH, substrate nature, and strain origin on protease, lipase, and hemolysin production. To achieve this objective, agar plate assays were performed at pH 5.0, 6.5, and 7.5 with substrates suitable for the detection of each family of enzymes. Moreover, the study was conducted with 20 clinical C. albicans isolates from blood, oral cavity, skin, urine, and vagina. The hydrolytic zones formed around the colonies were further measured to calculate the Ez (enzymatic zone) indexes. We found that detection of proteases in skim milk agar plates was possible for most isolates only at pH 5 (80%) and pH 6.5 (75%), whereas BSA plates could confer protease detection exclusively at pH 5 (80%). Similarly, the percentage of isolates possessing lipolytic activities was higher at pH 5 (90%) than at pH 6.5 (70%) and pH 7.5 (35%). In contrast, hemolytic activities were detected in all isolates at pH 6.5 and 7.5 but not at pH 5. Further analysis revealed that some differences in the detected activities could potentially be attributed to the anatomical origin of these isolates. Collectively, these findings suggest that the pH of the site of infection might be critical for mimicking the microenvironment employed to experimentally discover the key virulence factors.

The Effect of Exposure to Candida Albicans Suspension on the Properties of Silicone Dental Soft Lining Material

“…The initial pH values of the culture medium used in our experiment also corresponded to the saliva recorded, which is normally ranged from 5.6 to 7.1, including for denture wearers [73,74]. However, the presence of Candida species promotes the lowering of pH values by producing cetate; pyruvate; formate; and propionate acids, which influence in vitro tests and under clinical conditions may activate candidal proteases; phospholipases; and collagenases, promoting tissue damage and subsequent invasion by yeast-like fungi [75,76]. The possibility of the pH values of the culture medium used in studies influencing the penetration of C. albicans into soft lining remains unknown.…”

The inhibitory effect of ketoconazole-loaded nanostructure hybrid lipid capsules on the growth and biofilm activity of C. albicans

“…3 Especially under acidic conditions, the growth of C. albicans is more vigorous, 25 and the expression level of phospholipase and other virulence factors significantly increases. [2][3][4]22,26 It has been reported that an acidic environment can reduce the antifungal activity of KET, and the low antifungal activities of crude KET are related possibly to the increase in its piperazine base protonation rate with a reduction in pH. 9 Therefore, we also evaluated the antifungal activity of KET and KET-nHLCs at pH 4.5 (Fig.…”

“…It is well established that C. albicans adapts to a wide range of pH environments, where low pH is often significant due to its relationship with serious infection. 1,2 Acidic environments increase the secretion of phospholipases and other virulence factors, which contribute to the invasion of host tissues. [2][3][4] pH is also a potent regulator of the transition of yeast into filamentous hyphae, where an acidic environment favors yeast growth, while neutral and alkaline environments favor hyphae growth and biofilm formation.…”

“…1,2 Acidic environments increase the secretion of phospholipases and other virulence factors, which contribute to the invasion of host tissues. [2][3][4] pH is also a potent regulator of the transition of yeast into filamentous hyphae, where an acidic environment favors yeast growth, while neutral and alkaline environments favor hyphae growth and biofilm formation. 5,6 The mycelium plays an important role in the virulence of C. albicans and is responsible for the formation of biofilms, which are resistant to conventional antifungal therapeutics.…”

“…It is well known that the phospholipase secreted by C. albicans can degrade the phospholipid components of host cells, causing host cell damage. [2][3][4] In nHLCs, Lipoid S-75, as a type of phospholipid, should be a substrate for the phospholipase secreted by C. albicans. Thus, the degradation of Lipoid S-75 will trigger the release of the antifungal drug in nHLCs and affect its antifungal activity against C. albicans.…”