Candida parapsilosis Cell Wall Proteome Characterization and Effectiveness against Hematogenously Disseminated Candidiasis in a Murine Model

Abstract

Candida parapsilosis poses huge treatment challenges in the clinical settings of South Africa, and often causes infections among immunocompromised patients and underweight neonates. Cell wall proteins have been known to play vital roles in fungal pathogenesis, as these are the first points of contact toward environments, the host, and the immune system. This study characterized the cell wall immunodominant proteins of pathogenic yeast C. parapsilosis and evaluated their protective effects in mice, which could add value in vaccine development against the rising C. parapsilosis infections. Among different clinical strains, the most pathogenic and multidrug-resistant C. parapsilosis isolate was selected based on their susceptibility towards antifungal drugs, proteinase, and phospholipase secretions. Cell wall antigens were prepared by β-mercaptoethanol/ammonium bicarbonate extraction from selected C. parapsilosis strains. Antigenic proteins were identified using LC-MS/MS, where 933 proteins were found, with 34 being immunodominant. The protective effect of the cell wall immunodominant proteins was observed by immunizing BALB/c mice with cell wall protein extracts. After the immunization and booster, the BALC/c mice were challenged with a lethal dose of C. parapsilosis. In vivo results demonstrated increased survival rates and lower fungal burden in vital organs in the immunized mice compared to the unimmunized mice, thereby confirming the immunogenic property of cell wall-associated proteins of C. parapsilosis. Therefore, these results advocated the potential of these cell wall proteins to act as biomarkers for the development of diagnostic assays and/or vaccines against infections caused by C. parapsilosis.

Keywords: BALB/c mice; Candida parapsilosis; cell wall proteins; vaccine development.

Figure 1

Bar graph showing gene ontology enrichment analysis of biological processes for the proteins identified in the cell wall extract. Biological processes that were common to <5% of the proteins were excluded from the chart.

Figure 2

Survival probability of cell wall protein immunized BALB/c mice. The survival proportion states the potency of cell wall protein extract in protection against infection caused C. parapsilosis. Mantel–Cox log-range test was used to compare the survival in different groups. HC = health control; CWP = cell wall protein; IC = infection control. p value < 0.005.

Figure 3

Analysis of fungal burden. The effect of cell wall protein extract against infection caused by C. parapsilosis. The fungal burden was expressed as geometric means of logarithmic values for CFU/mg of tissues. HC = health control; CWP = cell wall protein; IC = infection control. (*** p < 0.05).

Figure 4

Comparative analysis of histopathology of different tissue sections from healthy control, immunized, and C. parapsilosis-infected mice after 48 h. Tissue sections recovered post infections were stained with PAS. The mouse from the infection control group displayed a higher fungal burden. While the cell wall protein immunized mouse showed significantly reduced fungal burden. The black arrows indicate of C. parapsilosis cells in the target tissues while the brown arrows indicate the damages in the kidney.