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Clostridioides difficile DNA is the genetic material of the Gram-positive, anaerobic bacterium responsible for Clostridioides difficile infection (CDI), a major cause of antibiotic-associated diarrhea and pseudomembranous colitis [1, 2]. The genome includes the pathogenicity locus (PaLoc), which encodes the major virulence factors, toxins A (TcdA) and B (TcdB), as well as genes for spore formation and antibiotic resistance [2]. As a therapeutic target, the DNA is directly acted upon by nitroimidazole antibiotics such as metronidazole [1, 4]. In the anaerobic environment of the bacterium, these drugs are reduced to form short-lived, highly reactive nitroso-free radicals that interact with the DNA, causing helical structure destabilization and strand breakage, which ultimately leads to bacterial cell death [1, 4]. Furthermore, specific sequences within the C. difficile DNA, particularly the tcdB gene, serve as critical biomarkers for diagnostic nucleic acid amplification tests (NAATs) used to identify toxigenic strains in clinical settings [3, 5]. The integrity and replication of this DNA are essential for the pathogen's persistence and transmission within the healthcare environment [2].
Induction of DNA strand breaks and inhibition of DNA synthesis via reactive radical intermediates
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