Doctoral Degrees (Microbiology)

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Browsing Doctoral Degrees (Microbiology) by browse.metadata.advisor "Deane, Shelly May"

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    In vitro and In vivo characterization of Amyloliquecidin, a novel two-component lantibiotic produced by Bacillus amyloliquefaciens
    (Stellenbosch : Stellenbosch University, 2015-04) Van Staden, Anton Du Preez; Dicks, Leon Milner Theodore; Deane, Shelly May; Stellenbosch University. Faculty of Science. Dept. of Microbiology.
    ENGLISH ABSTRACT: Antimicrobial resistance is one of the major problems faced by the medical industry today. The ability of bacteria to rapidly acquire resistance against antibiotics and the over prescription and inappropriate use of antibiotics further exacerbate this crisis. Few new antimicrobials are, however, making it through the drug discovery pipeline. The search and development of novel and effective antimicrobials is therefore of the utmost importance. Lantibiotics are ribosomally synthesized cationic antimicrobial peptides with extensive post-translational modifications. They are active against a wide range of Gram-positive bacteria, including antibiotic-resistant strains. They are characterized by the presence of lanthionine and methyllanthionine rings and have been suggested as alternatives or for use in conjunction with antibiotics against resistant pathogens. Staphylococcus aureus is the most common bacteria isolated from skin and soft tissue infections (SSTIs). Strains of S. aureus have emerged with resistance against antibiotics with the most common being methicillin-resistant S. aureus (MRSA). Several lantibiotics are active against MRSA in vivo and have even shown superior activity to traditional antibiotics. Lantibiotics therefore show much promise for the treatment of SSTIs caused by resistant- and non-resistant S. aureus. In this study the bacterially diverse soil of the Fynbos in the Western Cape was screened for novel antimicrobials. Two antimicrobial producing Bacillus strains were isolated, Bacillus clausii AD1 and Bacillus amyloliquefaciens AD2. Both of these strains produce lantibiotics with B. clausii AD1 producing a known lantibiotic, clausin. B. amyloliquefaciens AD2 produces a novel two-component lantibiotic which was designated amyloliquecidin. The lantibiotic operon of amyloliquecidin was sequenced and annotated. All the genes required for successful production of amyloliquecidin are present in the operon. Amyloliquecidin was characterized in vitro and along with clausin is active against clinical strains of S. aureus (including MRSA), Enterococcus spp., Listeria spp. and beta-haemolytic streptococci. Amyloliquecidin has remarkable stability at physiological pH compared to nisin and clausin. A comparative in vivo murine infection model was used to evaluate the effectiveness of amyloliquecidin, nisin, clausin and Bactroban (commercial S. aureus topical treatment) in treating wound infections caused by S. aureus. All the lantibiotics proved to be just as effective as the Bactroban treatment. Furthermore, the tested lantibiotics did not have a negative influence on the wound closure rates of infected and non-infected wounds. Bactroban had a negative effect on wound healing compared to the lantibiotics. To our knowledge amyloliquecidin is the third two-component lantibiotic isolated from Bacillus. This study represents the first to test the effectiveness of amyloliquecidin in vivo and is one of a handful to test lantibiotics as topical treatments.