Combined Antibiofilm Activity of Synthetic Peptides and Antifungal Drugs Against Candida Spp.

Abstract

Introduction: Candida krusei and Candida albicans are biofilm-forming drug-resistant yeasts that cause bloodstream infections that can lead to death. Materials & methods: nystatin and itraconazole were combined with two synthetic peptides, PepGAT and PepKAA, to evaluate the synergistic effect against Candida biofilms. Additionally, scanning electron and fluorescence microscopies were employed to understand the mechanism behind the synergistic activity. Results: Peptides enhanced the action of drugs to inhibit the biofilm formation of C. krusei and C. albicans and the degradation of mature biofilms of C. krusei. In combination with antifungal drugs, peptides’ mechanism of action involved cell wall and membrane damage and overproduction of reactive oxygen species. Additionally, in combination, the peptides reduced the toxicity of drugs to red blood cells. Conclusion: These results reveal that the synthetic peptides enhanced the antibiofilm activity of drugs, in addition to reducing their toxicity. Thus, these peptides have strong potential as adjuvants and to decrease the toxicity of drugs.

Synergistic Antibiofilm Activity between Synthetic Peptides and Ciprofloxacin against Staphylococcus aureus

“…As reported in many other studies from our research group, synthetic peptides are not toxic to human red blood cells (HRBC) [10,12]. Additionally, it has been shown that during synergistic action, peptides, besides enhancing drugs' effects, also reduce their toxicity to HRBC [11,13].…”

“…The ROS overproduction was determined following the method described by Bezerra et al [13]. The assays were conducted as the same for PI analysis.…”

“…The hemolytic activities against A, B, and O types of human erythrocytes of peptides and ciprofloxacin alone or in combination were done following the methodology by Bezerra et al [13]. The concentrations of all solutions were the same as used in the synergism assays.…”

Antifungal therapy of Candida biofilms: Past, present and future

“…These include the use antimicrobial peptides, inhibitors of other components within the biofilm matrix ( i.e . extracellular DNA), the use of probiotics, hsp90 inhibition, as well as modulators of quorum sensing [ [87] , [88] , [89] , [90] , [91] , [92] , [93] ]. An interesting methodology being developed and applied to the Candida biofilm field is that of photodynamic therapy (PDT), where the inhibitory activity is mediated by the action of reactive oxygen species generated by the photoactivation of a photosensitizer by a light source [ [94] , [95] , [96] , [97] ].…”

Various Biomimetics as Antifungals

“…When developing biomimetics and some combinations with them, special attention is paid to minimizing their toxicity (or its complete absence) in relation to human/animal/plant cells, as well as to the type of antifungal effect (mechanism of action) on cells in order to avoid the development of resistance [76,145]. At the initial stage of such investigations, toxicity is assessed using modern computer modeling methods [146].…”