Masters Degrees (Microbiology)

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Browsing Masters Degrees (Microbiology) by Author "Booysen, Elzaan"

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    Characterization of a novel antibiotic isolated from Xenorhabdus khoisanae and encapsulation of vancomycin in nanoparticles
    (Stellenbosch : Stellenbosch University, 2018-03) Booysen, Elzaan; Dicks, Leon Milner Theodore; Sadie-Van Gijsen, Hanel; Stellenbosch University. Faculty of Science. Dept. of Microbiology.
    ENGLISH ABSTRACT: Periprosthetic joint infection (PJI) is the major cause of total joint arthroplasty failures and is often caused by methicillin-resistant Staphylococcus aureus (MRSA). The ability of these bacteria to rapidly acquire resistance against antibiotics has made it nearly impossible to treat these persistent infections. The number of novel antibiotics that have successfully completed clinical trials has declined rapidly in the last 50 years. The search for novel antibiotics and alternative delivery routes is thus of utmost importance. Entomopathogenic bacteria, living in close association with nematodes, are a potential source of novel antibiotics. One such genus, Xenorhabdus, produces a variety of secondary metabolites, including antimicrobial compounds. The majority of these compounds are active against numerous so-called multidrug resistant pathogens. Antibiotics produced by Xenorhabdus spp. may thus be an alternative treatment for PJI. Numerous drugs fail phase II and III clinical trials due to insolubility, toxicity and instability at pharmaceutically active levels. This can be overcome by encapsulating the therapeutic drugs in nanoparticles. The polymer poly(DL-lactide-co-glycolide) (PLGA) has significant attention as a colloidal drug delivery device and is well-known for its biocompatibility. In this study, Xenorhabdus khoisanae was screened for the production of novel antibiotics. Three antibiotics were isolated from a X. khoisanae culture, two were similar to xenocoumacin-2 and one a novel antibiotic with a mass-to-charge ratio of 671, designated rhabdin. Rhabdin is active against two clinical strains of S. aureus (including MRSA). The osteogenic and cytotoxic effects of rhabdin were evaluated on two populations of rat femora-derived mesenchymal stem cells (MSC). Rhabdin was cytotoxic to the bone marrow-derived mesenchymal stem cells (bmMSC) at concentrations exceeding 3.5 μg/ml, but had no anti-osteogenic effects. In contrast, rhabdin was completely cytotoxic to proximal femur-derived mesenchymal stem cells (pfMSC). Vancomycin, traditionally used to treat MRSA, was also evaluated and no cytotoxicity was observed in bmMSC or pfMSC, but vancomycin had an anti-osteogenic effect on pfMSC. Vancomycin was encapsulated in PLGA nanoparticles (VNP) by electrospraying. The mean hydrodynamic diameter of VNP was 247 nm. The antimicrobial activity of free vancomycin and encapsulated vancomycin was compared and VNP showed enhanced antimicrobial activity. Vancomycin release was monitored for 10 days and followed first-order release. After10 days, only 50% of the encapsulated vancomycin was released from the nanoparticles. To our knowledge, this is the first study to report on antibiotics produced by X. khoisanae, the anti-osteogenic effects of vancomycin and the encapsulation of vancomycin in PLGA nanoparticles by electrospraying.