Clostridium difficile transcriptomics and metronidazole resistance
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Date
2012-09-28
Authors
Zhang, Jason J.
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Abstract
This is a two-part project. Proton pump inhibitors (PPIs) have been associated with increased risk of C. difficile infections and increased toxin production when combined with antimicrobial therapy. The first part of this project involved characterization of a hypervirulent NAP1 C. difficile strain, including genome sequencing and assembly, and the development of methods to study its transcriptomics using RNA-Seq, which will enable future researchers to study different expression patterns when toxigenic C. difficile is challenged with PPIs and/or antimicrobials in vitro. The second part of this project involved characterizing a clinical isolate of a NAP1 C. difficile displaying a markedly elevated MIC to metronidazole (MIC = 16 mg/mL), which initially exhibited MIC of 32 mg/mL. A method of obtaining a metronidazole-susceptible revertant from this isolate was developed and a revertant was obtained. The genomes of both isolates were sequenced, assembled, and aligned, then compared to each other for polymorphisms.
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Keywords
Clostridium, difficile, transcriptomics, CDI, CDAD, metronidazole, resistance, PPI, transcriptome, RNA-seq, NAP1, NAP2, PFGE, 454, pyrosequencing, MIC, microcolony, microcolonies, heteroresistance