Genomic surveillance of Clostridioides difficile transmission and virulence in a healthcare setting

作者：Erin Newcomer, Skye R. S. Fishbein, Kailun Zhang, Tiffany Hink, Kimberly A. Reske, Candice Cass, Zainab Hassan Iqbal, Emily Struttmann, Carey‐Ann D. Burnham, Erik R. Dubberke, Gautam Dantas · 发表于：mBio · 年份：2024 · DOI：10.1128/mbio.03300-23 · 被引用次数：13 · 研究领域：Clostridium difficile and Clostridium perfringens research、Viral gastroenteritis research and epidemiology、Nosocomial Infections in ICU

ABSTRACT Clostridioides difficile infection (CDI) is a major cause of healthcare-associated diarrhea, despite the widespread implementation of contact precautions for patients with CDI. Here, we investigate strain contamination in a hospital setting and the genomic determinants of disease outcomes. Across two wards over 6 months, we selectively cultured C. difficile from patients ( n = 384) and their environments. Whole-genome sequencing (WGS) of 146 isolates revealed that most C. difficile isolates were from clade 1 (131/146, 89.7%), while only one isolate of the hypervirulent ST1 was recovered. Of culture-positive admissions ( n = 79), 19 (24%) patients were colonized with toxigenic C. difficile on admission to the hospital. We defined 25 strain networks at ≤2 core gene single nucleotide polymorphisms; two of these networks contain strains from different patients. Strain networks were temporally linked ( P < 0.0001). To understand the genomic correlates of the disease, we conducted WGS on an additional cohort of C. difficile ( n = 102 isolates) from the same hospital and confirmed that clade 1 isolates are responsible for most CDI cases. We found that while toxigenic C. difficile isolates are associated with the presence of cdtR , nontoxigenic isolates have an increased abundance of prophages. Our pangenomic analysis of clade 1 isolates suggests that while toxin genes ( tcdABER and cdtR ) were associated with CDI symptoms, they are dispensable for patient colonization. T...