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Future of Engineered Phage Therapy for Clostridium difficile Infections
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Bacteriophages have the potential to eliminate both antibiotic-resistant and sensitive bacteria; as a result, they have become a major focus of such research. In contrast to antibiotics, which assault the entire bacterial population without discrimination, bacteriophages have a limited set of characteristics that allow them to target infectious microbes while avoiding friendly species (commensal microbiota). Nevertheless, large groups of naturally occurring bacteriophages that are well-differentiated and selective for the most clinically recognized pathogenic bacterial strains are required. Utilizing genetic engineering techniques that modify the target phage genome to synthesize phages with known characteristics in a brief period of time and at a low acquisition, characterization, and treatment cost. Clostridioides difficile is the leading cause of nosocomial acquired diarrhea, causing approximately 500,000 cases of Clostridium difficile infection (CDI) and nearly 29,000 deaths annually in the United States. It is believed that vancomycin contributes to the disruption of the gut microbiota, resulting in decreased colonization resistance against CDI and increased recurrence rates due to the continuous disruption of the gut microbiota. This article provides a concise summary of existing CRISPR-Cas systems that can be utilized to create a lytic phage as a potential treatment for CDIs. While additional research is required, phage treatment shows promise as a targeted and possibly more sustainable method of preventing severe C. difficile infections.

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