<i>Clostridioides difficile</i>: innovations in target discovery and potential for therapeutic success

Monaghan, Tanya; Seekatz, Anna M.; Mullish, Benjamin H.; Moore-Gillon, Claudia; Dawson, Lisa F.; Ahmed, Ammar; Kao, Dina; Chan, Weng C.

doi:10.1080/14728222.2021.2008907

Cited by 5 publications

(4 citation statements)

References 132 publications

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“…Phage therapy is an experimental treatment for CDI which involves the use of bacteriophages; viruses selected to target and kill C. difficile bacteria. In preclinical studies, phage-based therapy has shown promise in inhibiting spore outgrowth in vitro [111][112][113][114][115][116][117][118]. For instance, Mondal et al identified that recombinantly expressed cell wall hydrolase lysin from C. difficile phage phiMMPo1 was active against C. difficile [113].…”

Section: Emerging Therapiesmentioning

confidence: 99%

“…This could potentially reduce the risk of rCDI. The challenges with phage therapy include its stability in the gastrointestinal tract, the need to select and match phages to specific C. difficile strains, potential for phage resistance over time, and the need for ongoing research to determine the optimal administration strategies [111][112][113][114][115][116][117][118]. There are further promising pre-clinical data on emerging therapies in clinical trials which have been reviewed elsewhere [117].…”

Section: Emerging Therapiesmentioning

confidence: 99%

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Insights into the Evolving Epidemiology of Clostridioides difficile Infection and Treatment: A Global Perspective

et al. 2023

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Clostridioides difficile remains an important public health threat, globally. Since the emergence of the hypervirulent strain, ribotype 027, new strains have been reported to cause C. difficile infection (CDI) with poor health outcomes, including ribotypes 014/020, 017, 056, 106, and 078/126. These strains differ in their geographic distribution, genetic makeup, virulence factors, and antimicrobial susceptibility profiles, which can affect their ability to cause disease and respond to treatment. As such, understanding C. difficile epidemiology is increasingly important to allow for effective prevention measures. Despite the heightened epidemiological surveillance of C. difficile over the past two decades, it remains challenging to accurately estimate the burden and international epidemiological trends given the lack of concerted global effort for surveillance, especially in low- and middle-income countries. This review summarizes the changing epidemiology of C. difficile based on available data within the last decade, highlights the pertinent ribotypes from a global perspective, and discusses evolving treatments for CDI.

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Section: Emerging Therapiesmentioning

confidence: 99%

Section: Emerging Therapiesmentioning

confidence: 99%

Insights into the Evolving Epidemiology of Clostridioides difficile Infection and Treatment: A Global Perspective

et al. 2023

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“…Although there is limited understanding, Monaghan and colleagues demonstrated the upregulation of microRNAs (miRNAs) following FMT in mice models and RCDI patients. Specifically, miR-26b, miR-23a, miR-150, and miR-28-5p were upregulated following successful FMT, leading to a reduced expression of the following inflammatory gene targets: FGF-21, IL-12B, IL-18, and TNFRSF9 [25]. These changes may confer protective advantages against C. difficile-mediated damage to the intestinal epithelium.…”

Section: Introductionmentioning

confidence: 99%

In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection

et al. 2023

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Importance: Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. Aim: The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT. Methods: Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT. Results: Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition. Conclusion: Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms.

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“…Our current understanding of disease pathogenesis is that CDI is a multifactorial disease process dictated by pathogenic C. difficile toxin production, gut microbial dysbiosis, and altered host inflammatory responses [3]. The increased incidence of primary infection, occurrence of hypertoxigenic ribotypes, and more frequent occurrence of drug resistant, recurrent, and non-hospital CDI underscore the urgent unmet need to develop new therapeutics to tackle CDI [4]. Independent risk factors for CDI include advanced age, concomitant antibiotic use, gastric acid suppression, chemotherapy, corticosteroids, lymphoma or leukaemia, solid cancer or malignancy, chronic kidney disease, congestive heart disease, diabetes mellitus, chronic obstructive pulmonary disease, diverticular disease, inflammatory bowel disease, gastroesophageal reflux disease, peptic ulcer disease, nasogastric tube feeding, a stay in intensive care, non-surgical gastrointestinal procedures, and hospitalization [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

The Molecular Epidemiology of Clostridioides difficile Infection in Central India: A Prospective Observational Cohort Study

Biswas,

Pinkham,

Walk

et al. 2023

Microbiology Research

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This prospective observational cohort study aimed to establish and compare baseline rates of Clostridioides difficile infection (CDI) in community and hospitalized patients in Nagpur and rural Melghat Maharashtra, including adults aged ≥18 years with a diagnosis of diarrhoea as defined as 3 or more loose stools in a 24 h period. All diarrhoeal samples were tested for CDI using the C. diff Quik Chek Complete enzyme immunoassay. C. difficile-positive stool samples were characterised by toxigenic culture, antimicrobial susceptibility testing and PCR ribotyping. C. difficile testing was performed on 1683 patients with acute diarrhoea. A total of 54 patients (3.21%; 95% CI: 2.42–4.17) tested positive for both the GDH antigen and free toxin. The risk factors for CDI included the presence of co-morbidities, antibiotic usage, and immunosuppression. The detected PCR ribotypes included 053-16, 017, 313, 001, 107, and 216. Our findings show that toxigenic C. difficile is an important but neglected aetiologic agent of infective diarrhoea in Central India. These results underscore the need to enhance the awareness and testing of patients with diarrhoea in India regarding the presence of toxigenic C. difficile, particularly in high-risk individuals with multiple co-morbidities, immunosuppression, and recent or ongoing antibiotic exposure or hospitalization.

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Clostridioides difficile: innovations in target discovery and potential for therapeutic success

Cited by 5 publications

References 132 publications

Insights into the Evolving Epidemiology of Clostridioides difficile Infection and Treatment: A Global Perspective

Insights into the Evolving Epidemiology of Clostridioides difficile Infection and Treatment: A Global Perspective

In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection

The Molecular Epidemiology of Clostridioides difficile Infection in Central India: A Prospective Observational Cohort Study

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