The Mould War: Developing an Armamentarium against Fungal Pathogens Utilising Thymoquinone, Ocimene, and Miramistin within Bacterial Cellulose Matrices.

Sam Swingler,Grazyna Adamus,Abhishek Gupta,Wayne Heaselgrave,Iza Radecka,Marek Kowalczuk,Hazel Gibson

doi:10.3390/ma14102654

Abstract

An increase in antifungal resistance has seen a surge in fungal wound infections in patients who are immunocompromised resulting from chemotherapy, disease, and burns. Human pathogenic fungi are increasingly becoming resistant to a sparse repertoire of existing antifungal drugs, which has given rise to the need to develop novel treatments for potentially lethal infections. Bacterial cellulose (BC) produced by Gluconacetobacter xylinus has been shown to possess many properties that make it innately useful as a next-generation biopolymer to be utilised as a wound dressing. The current study demonstrates the creation of a pharmacologically active wound dressing by loading antifungal agents into a biopolymer hydrogel to produce a novel wound dressing. Amphotericin B is known to be highly hepatotoxic, which reduces its appeal as an antifungal drug, especially in patients who are immunocompromised. This, coupled with an increase in antifungal resistance, has seen a surge in fungal wound infections in patients who are immunodeficient due to chemotherapy, disease, or injury. Antifungal activity was conducted via Clinical & Laboratory Standards Institute (CLSI) M27, M38, M44, and M51 against Candida auris, Candida albicans, Aspergillus fumigatus, and Aspergillus niger. This study showed that thymoquinone has a comparable antifungal activity to amphotericin B with mean zones of inhibition of 21.425 ± 0.925 mm and 22.53 ± 0.969 mm, respectively. However, the mean survival rate of HEp-2 cells when treated with 50 mg/L amphotericin B was 29.25 ± 0.854% compared to 71.25 ± 1.797% when treated with 50 mg/L thymoquinone. Following cytotoxicity assays against HEp-2 cells, thymoquinone showed a 71.25 ± 3.594% cell survival, whereas amphotericin B had a mean cell survival rate of 29.25 ± 1.708%. The purpose of this study was to compare the efficacy of thymoquinone, ocimene, and miramistin against amphotericin B in the application of novel antifungal dressings.

Highlights

Wounds from various sources that have been in a prolonged state of irritation and rubor, with a high degree of exudate, are decidedly prone to becoming infected by various opportunistic and commensal organisms
The results show evidence that bacterial cellulose loaded with thymoquinone, o cellulose (n = 10, ±standard deviation (SD))
The results show evidence that bacterial cellulose loaded with thymoquinone, ocimene, or miramistin display antifungal activity against different species of Candida and Aspergillus

Summary

Introduction

Wounds from various sources that have been in a prolonged state of irritation and rubor, with a high degree of exudate, are decidedly prone to becoming infected by various opportunistic and commensal organisms. The typical approach in treating these wounds is to reduce infection and increase more favourable conditions at the wound site for healing, encouraging a more suitable environment for successful re-epithelisation and angiogenesis [1,2]. Immunodeficiency arising from burn injuries poses a genuine and present threat to the successful healing of patients. The central difficulty in burn patients is the burn wound itself. The body as a whole reacts to a burn dependent on severity, thickness, and coverage, those with thermal injuries that are extensive typify a whole-body reaction. As a result of this reaction, the inflammation arising from the injury mandates that the wound is protected from infection and that there is a timely closure of the exposed areas

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