Dataset Information

Translational Aspects of the Immunology of Clostridioides difficile Infection: Implications for Pediatric Populations.

ABSTRACT: Clostridioides difficile has become the most common healthcare-associated pathogen in the United States, leading the US Centers for Disease Control and Prevention (CDC) to classify C. difficile as an "urgent" public health threat that requires "urgent and aggressive action." This call to action has led to new discoveries that have advanced our understanding of Clostridioides difficile infection (CDI) immunology and clinical development of immunologic-based therapies for CDI prevention. However, CDI immunology research has been limited in pediatric populations, and several unanswered questions remain regarding the function of host immune response in pediatric CDI pathogenesis and the potential role of immunologic-based therapies in children. This review summarizes the innate and adaptive immune responses previously characterized in animals and humans and provides a current update on clinical development of immunologic-based therapies for CDI prevention in adults and children. These data inform the future research needs for children.

SUBMITTER: Kociolek LK

PROVIDER: S-EPMC8600028 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Translational Aspects of the Immunology of Clostridioides difficile Infection: Implications for Pediatric Populations.

Kociolek Larry K LK Zackular Joseph P JP Savidge Tor T

Journal of the Pediatric Infectious Diseases Society 20211101 Supplement_3

Clostridioides difficile has become the most common healthcare-associated pathogen in the United States, leading the US Centers for Disease Control and Prevention (CDC) to classify C. difficile as an "urgent" public health threat that requires "urgent and aggressive action." This call to action has led to new discoveries that have advanced our understanding of Clostridioides difficile infection (CDI) immunology and clinical development of immunologic-based therapies for CDI prevention. However, ...[more]

PMID: 34791392

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Project description:ObjectivesCarriage of Clostridioides difficile by different species of animals has led to speculation that animals could represent a reservoir of this pathogen for human infections. The objective of this study was to compare C. difficile isolates from humans, dogs, and cattle from a restricted geographic area.MethodsC. difficile isolates from 36 dogs and 15 dairy calves underwent whole genome sequencing, and phenotypic assays assessing growth and virulence were performed. Genomes of animal-derived isolates were compared to 29 genomes of isolates from a pediatric population as well as 44 reference genomes.ResultsGrowth rates and relative cytotoxicity of isolates were significantly higher and lower, respectively, in bovine-derived isolates compared to pediatric- and canine-derived isolates. Analysis of core genes showed clustering by host species, though in a few cases, human strains co-clustered with canine or bovine strains, suggesting possible interspecies transmission. Geographic differences (e.g., farm, litter) were small compared to differences between species. In an analysis of accessory genes, the total number of genes in each genome varied between host species, with 6.7% of functional orthologs differentially present/absent between host species and bovine-derived strains having the lowest number of genes. Canine-derived isolates were most likely to be non-toxigenic and more likely to carry phages. A targeted study of episomes identified in local pediatric strains showed sharing of a methicillin-resistance plasmid with dogs, and historic sharing of a wide range of episomes across hosts. Bovine-derived isolates harbored the widest variety of antibiotic-resistance genes, followed by canine CONCLUSIONS: While C. difficile isolates mostly clustered by host species, occasional co-clustering of canine and pediatric-derived isolates suggests the possibility of interspecies transmission. The presence of a pool of resistance genes in animal-derived isolates with the potential to appear in humans given sufficient pressure from antibiotic use warrants concern.

Dataset Information

Translational Aspects of the Immunology of Clostridioides difficile Infection: Implications for Pediatric Populations.

Publications

Translational Aspects of the Immunology of Clostridioides difficile Infection: Implications for Pediatric Populations.

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