Impact of Brief Exposure to Drugs with Antifungal Properties on the Susceptibility of Oral <b><i>Candida dubliniensis</i></b> Isolates to Lysozyme and Lactoferrin

Abstract

Objective: Lysozyme and lactoferrin have anti-candidal activity. Candida dubliniensis is associated with oral candidiasis. Candida infections are managed with nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine. Candida species undergo a brief exposure to therapeutic agents in the mouth. There is no data on the influence of limited exposure to antimycotics on the sensitivity of C. dubliniensis to lactoferrin and lysozyme. Hence, this study observed the changes in the sensitivity of C. dubliniensis to anti-candidal action of lactoferrin and lysozyme after transitory exposure to sub-lethal concentrations of antifungals. Materials and Methods: After determination of the minimum inhibitory concentration (MIC), 20 C. dubliniensis isolates were exposed to twice the concentration of MIC of nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine for 1 h. Drugs were removed by dilution and thereafter the susceptibility of these isolates to lysozyme and lactoferrin was determined by colony-forming unit quantification assay. Results: Exposure of C. dubliniensis to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine resulted in an increase in susceptibility to lysozyme by 9.45, 30.82, 30.04, 50.64, 55.60, and 50.18%, respectively (p < 0.05 to p < 0.001). Exposure of C. dubliniensis to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine resulted in an increase in susceptibility to lactoferrin by 13.54, 16.43, 17.58, 19.60, 21.32, and 18.73, respectively (p < 0.05 to p < 0.001). Conclusion: Brief exposure to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine enhances the antifungal effect of lysozyme and lactoferrin on C. dubliniensis isolates in vitro.

Alternative Treatment Strategies for Secondary Bacterial and Fungal Infections Associated with COVID-19

“…Acceptable sources of bovine and recombinant human lactoferrins are accessible for commercial applications, although further research is required for its medicinal use [ 94 ]. Their microbial activity has been shown to be very broad in nature due to their ability to sequester ferric ions [ 95 , 96 ]. Some clinical studies showed that oral administration of bovine lactoferrins can significantly reduce an already established candidiasis in mice.…”

Bovine Lactoferrin and Current Antifungal Therapy Against Candida Albicans: A Systematic Review and Meta-Analysis

“…This is thought to be related to the fungal cell wall’s surface structure and LF’s antifungal mechanism, which targets the cell wall proteins. [ 15 19 20 ] A study by Lee and Lee[ 21 ] showed that this cation peptide attaches to the charged plasma membrane negatively, which causes the transmembrane pore-like structure formation that resembles an ion channel. In this case, cell membrane permeabilisation leads to intracellular cell organelles leakage, ending in cell apoptosis.…”

“…Thus, it had no opportunities to describe the sensitivity of C. albicans higher had isolated to LF pre-exposed to drugs through antifungal agents. [ 19 23 ]…”

Lactoferrin: A Glycoprotein Involved in Immunomodulation, Anticancer, and Antimicrobial Processes

“…Lf, together with lactoferricin, lactoferrampin and the N-terminal region (Lf 1-11), has shown activity against different species of Candida by altering its cell wall and generating surface blebs, which cause cell death [ 126 , 127 ]. Likewise, Lf has been used in synergy with different antifungal drugs against different yeasts such as C. dubliniensis, C. albicans, C. glabrata, and Cryptococcus , where their effect is enhanced [ 128 , 129 ]. In the same context, Lf activity against Candida albicans was also enhanced when it was expressed in Lactobacillus casei , a member of the vaginal microbiota [ 130 ].…”