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Candice Bentley Recitation Tues. 1:50-2:45 Question: What types of variants are emerging as antibiotic resistant in Clostridium difficile and why? (Evolution of antibiotic resistance in C. difficile) Annotated Bibliography:

He M, et. al. (2010) Evolutionary dynamics of Clostridium difficile over short and long time scales. PNAS 107: 7527-7532. This study focuses on the genetic diversity of C. difficile based on phylogenetic analyses. They used genome sequencing to analyze virulence of different isolates of the disease. They find and explain how virulence evolved independently in the multiple lineages. This explains variants based on phylogeny, and their origin.

Lawley TD, et. al. (2009) Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores. J Bacteriology 191: 5377-5386. This experiment studies the spores of C. difficile. They purified the spores and demonstrated the resistance to physical and chemical treatments. They also examine the composition and biological properties of these spores, which helps us understand the reason and evolution for antibiotic resistance.

Spigaglia P, et. al. (2011) Multidrug resistance in European Clostridium difficile clinical isolates. Journal of Antimicrobial Chemotherapy 66: 2227-2234. This experiment studies multidrug resistance and antibiotic resistance in different strains of C. difficile. They show which strains are resistant to which drugs and specifically why they are so. They conclude that mutation is the cause of resistance, but also that antibiotic resistance is evolving in the pathogen.

Stabler RA, et. al. (2006) Comparative phylogenomics of Clostridium difficile reveals clade specificity and microevolution of hypervirulent strains. J Bacteriology 188: 7297-7305. This study, from the Journal of Bacteriology, examines hypervirulent strains of C. difficile. They explored genetic differences among clades, and found that antibiotic resistance is due to a genetic difference. They confirm that genetic exchange is a major factor in the evolution of this disease.

Tenover FC, et. al. (2012) Antimicrobial-resistant strains of Clostridium difficile from North America. Antimicrobial Agents and Chemotherapy 56: 2929-2932. The authors of this study are from Cepheid in California. They explored several different clinical isolates of C. difficile in North America, and screened them for resistance to certain antibiotics. They showed which ribotypes were resistant to only specific antibiotics and others that were multidrug resistant. This study shows differences in strain types and rates of resistance.