Investigation of Anti-Adherence and Antimicrobial Properties of Prodigiosin-Functionalized Bacterial Cellulose Membrane for Biomedical Applications

The beneficial applications of microbial secondary metabolites in the biomedical field that show potential antibacterial and antifungal activities, have become a fascinating alternative to prevent the development of antibiotic resistant microorganisms emerged due to the overuse/misuse of antibiotics (Hazarika et al., 2021, Islan et al., 2022). According to the latest reports of the World Health Organization (WHO), multi-drug resistant (MDR) and extreme drug resistant (XDR) strains are predicted to cause the death up to 10 million people every year, unless appropriate measures are taken by 2050 (WHO, 2017). Therefore, investigating the biological properties of microbial metabolites such as a bacterial pigment prodigiosin (PG), known with magnificent bioactive features, will contribute to the development of novel drugs. Red alkaloid pigment-PG which shows several bioactivities such as antimicrobial, antimalarial, algicidal, antiparasitic and anticancer, is secreted mostly by Serratia marcescens (S. marcescens) and other some microorganisms as a secondary metabolite (Gohil et al., 2020). PG can show antimicrobial activity against many bacteria and fungi that are the main cause of various infections or food spoilage (Hazarika et al., 2021). This information paves the way for the use of PG as a promising antimicrobial agent for wound healing or food packaging applications. In addition, the production of PG through bacterial fermentation process has a capability to reach high yields with using cheap and easy-available substrates and low amounts of residues (Bhagwat and Padelia, 2020). However, the low solubility and high hydrophobicity of PG are sometimes seen as challenges limiting its use. To overcome these drawbacks, it is suggested to use PG by immobilizing with nanoparticles, hydrogels, and polymers for developing new bioactive materials (Islan et al., 2022).

Bacterial cellulose (BC) which is an adaptable and easily modified natural polymer with its unique features such as high porosity, web-like structure, immense water holding capacity, high degree of polymerization, excellent biological affinity, non-toxicity, and biocompatibility, has been reported as a useful biomaterial for several fields from medicine to industry (Graser and Avcioglu, 2022; Shrivastav et al., 2022). However, although BC is a leading biomaterial with its fascinating physicochemical properties, enabling new medicinal applications, poor bioactivity of its native form restricts the applicability of BC in the various biomedical approaches. While developing a wound dressing, BC is a useful dressing material that promote wound healing by maintaining wet environment and holding wound exudate. However, the lack of antimicrobial effect of BC limits its use as a scaffold. Hence, to impart the antimicrobial features to BC, BC-based nanocomposite materials were prepared by functionalizing with antimicrobial agents. In recent studies, antibiotic loaded BC materials (Tamahkar et al., 2019, Ye et al., 2018) or BC composites functionalized with essential oils (Nagmateva et al., 2020) or antimicrobial peptides (Fürsatz et al., 2018) were developed as a wound dressing or drug delivery system.

Based on the versatile characteristics of BC and PG, the present study was focused on developing a novel biomaterial that can be used as a wound dressing material by functionalizing BC with PG. In the first step, enhanced PG production was realized with S. marcescens and after extraction-purification processes to obtain pure PG, characterization, antimicrobial and antibiofilm activity studies were completed. On the one hand, optimized BCMs were produced and purified according to Avcioglu et al. (Avcioglu et al., 2021). In this study, the lack of bioactivity of BCM that limits its use in biomedical applications have been overcome by incorporating with PG. Afterwards, PG-BCM was characterized, and in vitro cytotoxicity test was performed. Then antibacterial and antifungal properties were determined. The results revealed the benefits of natural compounds with antimicrobial properties obtained from microorganisms after low-cost fermentation processes in the development of new functional biomaterials.

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