Identification of Clostridium innocuum hypothetical protein that is cross-reactive with C. difficile anti-toxin antibodies

Cherny, Kathryn E.; Balaji, Aakash; Mukherjee, Jayabrata; Goo, Young Ah; Hauser, Alan R.; Ozer, Egon A.; Satchell, K.J.F.; Bachta, Kelly E R; Kochan, Travis J.; Mitra, Sumitra D.; Kociolek, Larry K.

doi:10.1016/j.anaerobe.2022.102555

Cited by 10 publications

(7 citation statements)

References 31 publications

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“…The demonstrated genomic and phenotypic variability observed across the C. innocuum species may also be of clinical importance. C. innocuum is commonly isolated in conjunction with gastrointestinal tissue or fecal clinical samples (36,41,97). In summary, we demonstrate strain-specific variation of a prevalent gut 'commensal' that until recently was considered relatively benign in the gut environment.…”

Section: Discussionmentioning

confidence: 75%

“…An exotoxin has not been identified from C. innocuum despite previous evidence association with infection (97). Using PathoFact to identify potential virulence (bit score > 50), we observed differential distribution of putative virulence factors across the four clades (Figure 6A) (85).…”

Section: Resultsmentioning

confidence: 96%

“…The demonstrated genomic and phenotypic variability observed across the C. innocuum species may also be of clinical importance. C. innocuum is commonly isolated in conjunction with gastrointestinal tissue or fecal clinical samples (36, 41, 97). A recent retrospective study in a Taiwanese clinical cohort isolated C. innocuum rather than C. difficile from patients with C. difficile -like clinical presentation (36).…”

Section: Discussionmentioning

confidence: 99%

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Diversity and prevalence ofClostridium innocuumin the human gut microbiota

Bhattacharjee

Flores

Woelfel-Monsivais

et al. 2022

Preprint

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Clostridia are a polyphyletic group of Gram-positive, spore-forming anaerobes in the Firmicutes phylum that significantly impact metabolism and functioning of human gastrointestinal tract. Recently, Clostridia were divided into two separate classes, Clostridia and Erysipelotrichia, based on phenotypic and 16S rRNA gene-based differences. While Clostridia include many well-known pathogenic bacteria, Erysipelotrichia remain relatively uncharacterized, particularly regarding their role as a pathogen vs. commensal. Despite wide recognition as a commensal, the Erysipelotrichial species, Clostridium innocuum, has recently been associated with various disease states. To further understand the ecological and potential virulent role of C. innocuum, we conducted a genomic comparison across 38 C. innocuum isolates and 75 publicly available genomes. Based on colony morphology, we isolated multiple C. innocuum cultivars from the feces of healthy human volunteers (n=5). Comparison of the 16S rRNA gene of our isolates against publicly available microbiota datasets in healthy individuals suggests a high prevalence of C. innocuum across the human population (> 80%). Analysis of single nucleotide polymorphisms (SNPs) across core genes and average nucleotide identify (ANI) revealed the presence of 4 clades among all available unique genomes (n=108 total). Investigation of carbohydrate and protein utilization pathways, including comparison against the carbohydrate-activating-enzyme (CAZyme) database, demonstrated inter-and intra-clade differences that were further substantiated in vitro. Collectively, these data indicate genetic variance within the C. innocuum species that may help clarify its role in human disease and health.IMPORTANCEClostridia are a group of medically important anaerobes as both commensals and pathogens. Recently, a new class of Erysipelotrichia containing a number of re-assigned Clostridial species has emerged, including Clostridium innocuum. Recent studies have implicated C. innocuum as a potential causative agent of diarrhea in patients from whom Clostridioides difficile could not be isolated. Using genomic and in vitro comparison, this study sought to characterize C. innocuum in the healthy human gut. Our analyses suggest that C. innocuum is a highly prevalent and diverse species, demonstrating clade-specific differences in metabolism and potential virulence. Collectively, this study is the first investigation into a broader description of C. innocuum as a human gut inhabitant.

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Section: Discussionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 96%

“…The demonstrated genomic and phenotypic variability observed across the C. innocuum species may also be of clinical importance. C. innocuum is commonly isolated in conjunction with gastrointestinal tissue or fecal clinical samples (36, 41, 97). A recent retrospective study in a Taiwanese clinical cohort isolated C. innocuum rather than C. difficile from patients with C. difficile -like clinical presentation (36).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Diversity and prevalence ofClostridium innocuumin the human gut microbiota

Bhattacharjee

Flores

Woelfel-Monsivais

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…An exotoxin has not been identified from C. innocuum despite previous evidence of association with infection ( 66 ). Using PathoFact to identify potential virulence (bit score > 50), we observed differential distribution of putative virulence factors across the four clades ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The demonstrated genomic and phenotypic variability observed across the C. innocuum species may also be of clinical importance. C. innocuum is commonly isolated in conjunction with gastrointestinal tissue or fecal clinical samples ( 35 , 40 , 66 ). A recent retrospective study in a Taiwanese clinical cohort isolated C. innocuum rather than C. difficile from patients with C. difficile -like clinical presentation ( 35 ).…”

Section: Discussionmentioning

confidence: 99%