Breedge Callaghan

Bio: Breedge Callaghan is an academic researcher from Ulster University. The author has contributed to research in topics: Sophorolipid & Inflammasome. The author has an hindex of 2, co-authored 4 publications receiving 60 citations.

Adjuvant Antibiotic Activity of Acidic Sophorolipids with Potential for Facilitating Wound Healing

Abstract: The sophorolipid class of biosurfactants is finding increasing use in personal care as well as pharmaceutical products and has the potential to disrupt biofilm formation and inhibit the growth of a variety of clinically relevant organisms. In order to investigate potential biomedical applications of sophorolipids derived from nonpathogenic organisms, we fractionated and purified glycolipid biosurfactant sophorolipids produced by the yeast Starmerella bombicola, which yielded nonacetylated acidic C 18:1 congeners that were essentially free from other contaminants (>95% purity). These acidic sophorolipids have antimicrobial activities against the nosocomial infective agents Enterococcus faecalis and Pseudomonas aeruginosa, with significant reductions in CFU at concentrations of as low as 5 mg ml −1 . In addition, the sophorolipid showed similar effects against the same two bacterial strains when combined with kanamycin or cefotaxime. As a potential use of these sophorolipids is as a component of topically applied creams for the treatment of wound infections, it is clear that they must have no demonstrable adverse effect on wound healing. To assess this, we evaluated mammalian cell toxicity in vitro using viability tests, which revealed no adverse effect on either endothelial or keratinocyte-derived cell lines with sophorolipid concentrations of −1 . In addition, in vivo experiments using a mouse skin wounding assay revealed that the time course of healing wounds was unaffected by the application of sophorolipid-containing creams, and histological examination of regenerated skin tissue confirmed that the healing process was similar to that observed for control animals, with no evidence of inflammation. These results are consistent with the suggestion that acidic sophorolipids can be used as a component of antimicrobial creams to reduce the risk of wound infection during healing.

Lactonic Sophorolipids Increase Tumor Burden in Apcmin+/- Mice.

Abstract: Sophorolipids (SL) are amphiphilic biosurfactant molecules consisting of a disaccharide sophorose with one fatty acid at the C1 position and optional acetylation at the C6'and C6" positions. They exist in a closed ring lactonic (LSL) or open acidic (ASL) structure Sophorolipids are produced in crude mixtures in economically viable amounts by the yeast Starmerella bombicola and used in a variety of consumer products. Varying levels of anti- proliferative and anti-cancer activity of crude sophorolipid mixtures are described in a number of tumor cell lines in vitro. However, significant inter-study variation exists in the composition of sophorolipid species as well as other biologically active compounds in these mixtures, which makes interpretation of in vitro and in vivo studies difficult. We produced a 96% pure C18:1 lactonic sophorolipid that dose-dependently reduces the viability of colorectal cancer, as well as normal human colonic and lung cell lines in vitro. Oral administration of vehicle-only; or lactonic sophorolipids (50 mg/kg for 70 days), to Apcmin+/- mice resulted in an increase in the number (55.5 ± 3.3 vs 70.50 ± 7.8: p < 0.05) and size (modal size 2mm vs 4mm) of intestinal polyps. Lactonic administration resulted in a systematic effect via reduced hematocrit (49.5 ± 1.0 vs 28.2 ± 2.0 vs: p<0.03) and splenomegaly (0.56 ± 0.03g vs 0.71 ± 0.04g; p<0.01) confirming exacerbation of disease progression in this model.

Targeting the NLRP3 Inflammasome in Glaucoma.

Abstract: Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30-40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.

Abstract 2294: Sophorolipid-mediated inhibition of colorectal tumor cell growth in vitro and in vivo

Abstract: Background: Sophorolipids (SL), are amphiphilic biosurfactant molecules which consist of a sophorose molecule with 2 variable chain length (C10 - C22) They contain double bonds at the 3” 4” positions and fatty acids at the 1” positions. SL exist in either a lactonic (SLL; open ring) or acidic (SLA; closed ring) forms. SL is produced in crude mixtures by the yeast Candidia bombicola in economically viable amounts, with variable levels of anti-proliferative activity on tumour cell lines in vitro. As biosurfactants are well tolerated in the GI tract and currently used in a variety of food products, we tested the hypotheses that purified forms of either SLL or SLA have differential effects on colo-rectal tumour versus “normal” cells as well as in a well-established model of pre-cancerous lesions; viz the Apcmin+/− mouse. Methodology: The colo-rectal cancer cell lines HT29, HT115, HCT116, Caco-2 in addition to CCD-841 colonic epithelium and MRC5 lung fibroblasts were exposed to 10 - 100 μg/ml of either SLL or SLA (96% or 94%) pure respectively by HPLC/MS analysis) for 24 hours following serum starvation and an MTT assay performed. The mechanism of cell death in cell lines was assessed by acridine orange/ethidium bromide staining followed by microscopic examination. Five-week old APCmin+ mice or wild-type littermate mice were treated orally with 50mg/kg of either SLL or SLA, or vehicle-only control every other day for 14 weeks. Weights, water and food consumption were measured on a daily basis. On completion of the experiment, mice were euthanized, the digestive tract was excised, washed and fixed with 10% BFS. Polyp size, number and location were recorded and samples were blocked for paraffin embedding, sectioning and HE 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2294. doi:10.1158/1538-7445.AM2015-2294

Microbial biosurfactants: current trends and applications in agricultural and biomedical industries.

Abstract: Synthetic surfactants are becoming increasingly unpopular in many applications due to previously disregarded effects on biological systems and this has led to a new focus on replacing such products with biosurfactants that are biodegradable and produced from renewal resources. Microbially derived biosurfactants have been investigated in numerous studies in areas including: increasing feed digestibility in an agricultural context, improving seed protection and fertility, plant pathogen control, antimicrobial activity, antibiofilm activity, wound healing and dermatological care, improved oral cavity care, drug delivery systems and anticancer treatments. The development of the potential of biosurfactants has been hindered somewhat by the myriad of approaches taken in their investigations, the focus on pathogens as source species and the costs associated with large-scale production. Here, we focus on various microbial sources of biosurfactants and the current trends in terms of agricultural and biomedical applications.

Marine Biosurfactants: Biosynthesis, Structural Diversity and Biotechnological Applications.

Abstract: Biosurfactants are amphiphilic secondary metabolites produced by microorganisms. Marine bacteria have recently emerged as a rich source for these natural products which exhibit surface-active properties, making them useful for diverse applications such as detergents, wetting and foaming agents, solubilisers, emulsifiers and dispersants. Although precise structural data are often lacking, the already available information deduced from biochemical analyses and genome sequences of marine microbes indicates a high structural diversity including a broad spectrum of fatty acid derivatives, lipoamino acids, lipopeptides and glycolipids. This review aims to summarise biosyntheses and structures with an emphasis on low molecular weight biosurfactants produced by marine microorganisms and describes various biotechnological applications with special emphasis on their role in the bioremediation of oil-contaminated environments. Furthermore, novel exploitation strategies are suggested in an attempt to extend the existing biosurfactant portfolio.

Microbial Biosurfactants in Cosmetic and Personal Skincare Pharmaceutical Formulations

Abstract: Cosmetic and personal care products are globally used and often applied directly on the human skin. According to a recent survey in Europe, the market value of cosmetic and personal care products in Western Europe reached about 84 billion euros in 2018 and are predicted to increase by approximately 6% by the end of 2020. With these significant sums of money spent annually on cosmetic and personal care products, along with chemical surfactants being the main ingredient in a number of their formulations, of which many have been reported to have the potential to cause detrimental effects such as allergic reactions and skin irritations to the human skin; hence, the need for the replacement of chemical surfactants with other compounds that would have less or no negative effects on skin health. Biosurfactants (surfactants of biological origin) have exhibited great potential such as lower toxicity, skin compatibility, protection and surface moisturizing effects which are key components for an effective skincare routine. This review discusses the antimicrobial, skin surface moisturizing and low toxicity properties of glycolipid and lipopeptide biosurfactants which could make them suitable substitutes for chemical surfactants in current cosmetic and personal skincare pharmaceutical formulations. Finally, we discuss some challenges and possible solutions for biosurfactant applications.