Microbiologic factors affecting Clostridium difficile recurrence

Chilton, Caroline H.; Pickering, D.S.; Freeman, Joseph T.

doi:10.1016/j.cmi.2017.11.017

Cited by 58 publications

(42 citation statements)

References 100 publications

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“…Furthermore, ciprofloxacin, another efficient treatment for pouchitis, might be more effective in treating Fusobacteria than Bacteroidetes, based on MIC measurements [22]. In other circumstances, the sparing of anaerobic bacteria, such as Bacteroidetes, in the gut results in a higher clinical efficacy of antibiotic drugs used for gastrointestinal infections, e.g., it has been found to be important to preserve microbiota diversity when treating Clostridium difficile infection (CDI), so as to reduce the risk of recurrences [23].…”

Section: Discussionmentioning

confidence: 99%

High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation

et al. 2020

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Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.

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Section: Discussionmentioning

confidence: 99%

High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation

et al. 2020

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“…If conditions are favorable, e.g., after antibiotic-induced dysbiosis when the reduced microbiome fails to convert primary bile acids into secondary bile acids, C. difficile spores are able to germinate to successively colonize the large intestine ( Theriot et al, 2014 ; Pike and Theriot, 2020 ). Even though antibiosis mostly stops the acute infection, C. difficile spores as well as some vegetative cells survive in the intestine and can subsequently cause a relapse as soon as antibiotic concentrations are sufficiently low ( Goulding et al, 2009 ; Chilton et al, 2018 ; Castro-Córdova et al, 2020 ; Feuerstadt et al, 2021 ; Normington et al, 2021 ). Initially, sporulation was assumed to be one of the major prerequisites for C. difficile’s persistence under clinical circumstances.…”

Section: Introductionmentioning

confidence: 99%

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

et al. 2021

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The anaerobic pathogen Clostridioides difficile is perfectly equipped to survive and persist inside the mammalian intestine. When facing unfavorable conditions C. difficile is able to form highly resistant endospores. Likewise, biofilms are currently discussed as form of persistence. Here a comprehensive proteomics approach was applied to investigate the molecular processes of C. difficile strain 630Δerm underlying biofilm formation. The comparison of the proteome from two different forms of biofilm-like growth, namely aggregate biofilms and colonies on agar plates, revealed major differences in the formation of cell surface proteins, as well as enzymes of its energy and stress metabolism. For instance, while the obtained data suggest that aggregate biofilm cells express both flagella, type IV pili and enzymes required for biosynthesis of cell-surface polysaccharides, the S-layer protein SlpA and most cell wall proteins (CWPs) encoded adjacent to SlpA were detected in significantly lower amounts in aggregate biofilm cells than in colony biofilms. Moreover, the obtained data suggested that aggregate biofilm cells are rather actively growing cells while colony biofilm cells most likely severely suffer from a lack of reductive equivalents what requires induction of the Wood-Ljungdahl pathway and C. difficile’s V-type ATPase to maintain cell homeostasis. In agreement with this, aggregate biofilm cells, in contrast to colony biofilm cells, neither induced toxin nor spore production. Finally, the data revealed that the sigma factor SigL/RpoN and its dependent regulators are noticeably induced in aggregate biofilms suggesting an important role of SigL/RpoN in aggregate biofilm formation.

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“…Specifically, antibiotics represent the single greatest risk factor for the development of CDI, 19 , 20 given the ability of CD to expand its population in a dysbiotic gastrointestinal tract. 21 , 22 Even the use of recommended CD-directed antibiotics may exacerbate intestinal dysbiosis, 23 , 24 and multiple studies have demonstrated that commensal microorganisms may not return to “baseline” after CDI. 25 , 26 These effects from conventional antibiotics require more study in human subjects to evaluate whether they contribute to persistence or recurrence of CDI, though the often-long-lasting gut ecological disturbances invoked by conventional antibiotics represent a potential, clinically relevant unintentional consequence of therapy.…”

Section: Challenges To Conventional Antibiotic Therapies For mentioning

confidence: 99%

Anti-virulence strategies for Clostridioides difficile infection: advances and roadblocks

2020

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Clostridioides difficile infection (CDI) is a common healthcare- and antibiotic-associated diarrheal disease. If mis-diagnosed, or incompletely treated, CDI can have serious, indeed fatal, consequences. The clinical and economic burden imposed by CDI is great, and the US Centers for Disease Control and Prevention has named the causative agent, C. difficile (CD), as an Urgent Threat To US healthcare. CDI is also a significant problem in the agriculture industry. Currently, there are no FDA-approved preventives for this disease, and the only approved treatments for both human and veterinary CDI involve antibiotic use, which, ironically, is associated with disease relapse and the threat of burgeoning antibiotic resistance. Research efforts in multiple laboratories have demonstrated that non-toxin factors also play key roles in CDI, and that these are critical for disease. Specifically, key CD adhesins, as well as other surface-displayed factors have been shown to be major contributors to host cell attachment, and as such, represent attractive targets for anti-CD interventions. However, research on anti-virulence approaches has been more limited, primarily due to the lack of genetic tools, and an as-yet nascent (but increasingly growing) appreciation of immunological impacts on CDI. The focus of this review is the conceptualization and development of specific anti-virulence strategies to combat CDI. Multiple laboratories are focused on this effort, and the field is now at an exciting stage with numerous products in development. Herein, however, we focus only on select technologies (Figure 1) that have advanced near, or beyond, pre-clinical testing (not those that are currently in clinical trial), and discuss roadblocks associated with their development and implementation.

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Microbiologic factors affecting Clostridium difficile recurrence

Cited by 58 publications

References 100 publications

High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation

High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

Anti-virulence strategies for Clostridioides difficile infection: advances and roadblocks

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