Presentation (Project) Title

Comparative Genomics of C. Difficile Prophage-like Elements

Mentor Information

Xingmin Sun (College of Medicine)

Presentation Format

Event

Abstract

Clostridioides difficile is the main cause of nosocomial-acquired diarrhea and is a growing antibiotic resistance threat. The C. difficile genome contains numerous mobile genetic elements that have influenced the evolution and pathogenicity of the species. Bacteriophages that have integrated into the host bacterial genome, known as prophages, represent one type of mobile genetic element highly relevant to C. difficile virulence. Some prophages can extricate their DNA from the host genome to produce functional phage, while others remain permanently integrated due to mutations. Several functional C. difficile bacteriophages have been characterized, but little progress has been made to examine the diversity of prophages in thousands of C. difficile isolates. In this study, we used bioinformatics to characterize 53 putative prophages predicted in C. difficile genomes. After annotating each prophage, we conducted a comparative analysis of prophage genome structure, phylogeny, and virulence factor carriage. Phylogenetic analysis of the terL, terS, portal, and integrase sequences suggests different evolutionary patterns between important prophage genes. We demonstrated that prophages, just like their functional phage counterparts, share a common modular layout even in the absence of sequence similarity between individuals. Yet, there are still differences between prophage clusters and between prophages and functional phages. For example, prophages may contain duplicated genome modules, which are uncommon in functional phages. Analyzing prophage sequences could be used to reveal the evolution, virulence factor carriage, and other characteristics of their host bacteria. Novel therapeutics against C. difficile could also be developed from prophage genes with predicted antibacterial activity.

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Comparative Genomics of C. Difficile Prophage-like Elements

Clostridioides difficile is the main cause of nosocomial-acquired diarrhea and is a growing antibiotic resistance threat. The C. difficile genome contains numerous mobile genetic elements that have influenced the evolution and pathogenicity of the species. Bacteriophages that have integrated into the host bacterial genome, known as prophages, represent one type of mobile genetic element highly relevant to C. difficile virulence. Some prophages can extricate their DNA from the host genome to produce functional phage, while others remain permanently integrated due to mutations. Several functional C. difficile bacteriophages have been characterized, but little progress has been made to examine the diversity of prophages in thousands of C. difficile isolates. In this study, we used bioinformatics to characterize 53 putative prophages predicted in C. difficile genomes. After annotating each prophage, we conducted a comparative analysis of prophage genome structure, phylogeny, and virulence factor carriage. Phylogenetic analysis of the terL, terS, portal, and integrase sequences suggests different evolutionary patterns between important prophage genes. We demonstrated that prophages, just like their functional phage counterparts, share a common modular layout even in the absence of sequence similarity between individuals. Yet, there are still differences between prophage clusters and between prophages and functional phages. For example, prophages may contain duplicated genome modules, which are uncommon in functional phages. Analyzing prophage sequences could be used to reveal the evolution, virulence factor carriage, and other characteristics of their host bacteria. Novel therapeutics against C. difficile could also be developed from prophage genes with predicted antibacterial activity.