Identification of Bacteroides genes involved in Metronidazole resistance

• Main Author: Casanueva, Ana
• Other Authors: Abratt, Valerie Rose
• Format: Doctoral Thesis
• Language: English
• Published: University of Cape Town 2014
• Subjects: Cell Biology
• Online Access: http://hdl.handle.net/11427/4246

Includes bibliographical references (leaves [123]-141). === Bacteroides species are Gram-negative obligate anacrobes that live in the gastrointestinal tract of mammals and are thought to account for approximately 30% of the colonic microbiota. Certain Bacteroides species, such as B. fragilis and to a lesser extent B. thetaiotaomicron, can become opportunistic pathogens and cause severe infection. The antibiotic of choice for treating such infections is metronidazole, a DNA damaging agent. Metronidazole enters the bacterial cell as an inert prodrug, and is activated by cellular reduction into a cytotoxic compound which is thought to cause DNA strand breaks. Certain metronidazole resistant B. fragilis strains have been described, where the drug was not reduced inside the cell due to decreased activity of the metabolic enzymes which are involved in this process. Little is known about the mechanisms involved in repair of metronidazole damage and the potential for resistance. In this study, two difIerent approaches were used to isolate and analyse Bacteroides genes involved in metronidazole resistance, with emphasis on DNA repair genes. These methods were transposon mutagenesis of Bacteroides, and functional complementation of E. coli metronidazole sensitive mutants with genes from B. fragilis.