Abstract
Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the need for combinational therapies. Tyrocidines are cyclic antimicrobial peptides that have shown synergistic activity with antifungal drugs such as caspofungin and amphotericin B. However, these cyclodecapeptides have haemolytic activity and cytotoxicity, but they have been used for decades in the clinic for topical applications. The tyrocidines tend to form higher-order structures in aqueous solutions and excessive aggregation can result in variable or diminished activity. Previous studies have shown that the tyrocidines prefer ordered association to celluloses. Therefore, a formulation with soluble cellulose was used to control the oligomer stability and size, thereby increasing the activity against Candida spp. Of the formulants tested, it was found that commercial hydroxy-propyl-methyl cellulose, E10M, yielded the best results with increased stability, increased anti-Candida activity, and improved selectivity. This formulation holds promise in topical applications against Candida spp. infections.
Highlights
Out of 350 heterogeneous Candida species, more than 17 different Candida species are responsible for human and animal infections
A recent study showed that tryptocidine C, a Trp-rich analogue found in the Tyrocidine mixture (Trc mix), formed defined nanoparticles and that the oligomerisation can be followed by electrospray Antibiotics 2021, 10, x FOR PEER REVmIEaWss spectrometry and fluorescence [40]
The target organism in this study was an environmental strain of C. albicans CAB1653 that was isolated from mosquito larvae. We found that this strain was completely resistant towards fluconazole, while it exhibited minimum inhibition concentration (MIC) of 9 mM and mM against caspofungin and amphotericin B, respectively, after a h challenge
Summary
Out of 350 heterogeneous Candida species, more than 17 different Candida species are responsible for human and animal infections. Candida spp. can quickly adapt to new and challenging environments in nature. They can use different nutritional resources and express different metabolic pathways for optimal survival. The recent emergence of fungi that are resistant to more than one class of antifungal drug is a serious concern. Polyenes (i.e., amphotericin B), azoles (i.e., fluconazole) and echinocandins (i.e., caspofungin) are the main antifungal drug classes used to treat fungal infections [5]. If an antifungal drug class becomes ineffective in treating a fungal infection, it reduces the therapeutic options by at least 33%, and in the most severe resistance cases, clinicians are left with no treatment options
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