The molecular basis of Clostridium difficile disease and host response

Feghaly, Rana E. El; Bangar, Hansraj

doi:10.1097/mog.0000000000000131

Cited by 19 publications

(15 citation statements)

References 52 publications

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“…However, the host factors that determine CDI severity remain poorly characterized [29]. To investigate the impact of MIF on CDI disease severity, mice were given intraperitoneal (i.p.)…”

Section: Resultsmentioning

confidence: 99%

Neutralization of macrophage migration inhibitory factor improves host survival after Clostridium difficile infection

et al. 2018

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Clostridium difficile is an important cause of nosocomial diarrhea in the western world. Toxins (A, B, and binary toxins) generated by C. difficile bacteria damage intestinal epithelial cells. Hallmarks of host response to C. difficile infection (CDI) include upregulation of inflammatory mediators and tissue infiltration by immune cells. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that is known to enhance the host immune response to infectious pathogens. Additionally, MIF can adversely impact host survival to numerous infections. The role of MIF in the pathogenesis of CDI remains poorly understood. Here, we show that patients with CDI had significantly higher circulating MIF compared to patients who had diarrhea but tested negative for C. difficile (non-CDI controls). Similarly, in a mouse model, C. difficile challenge significantly increased levels of plasma and tissue MIF. Antibody-mediated depletion of MIF decreased C. difficile-induced inflammatory responses, clinical disease, and mortality. Together, these results uncover a potential role for MIF in exacerbating CDI and suggest that use of anti-MIF antibodies may represent a therapeutic strategy to curb host inflammatory responses and improve disease outcomes in CDI.

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“…However, the host factors that determine CDI severity remain poorly characterized [29]. To investigate the impact of MIF on CDI disease severity, mice were given intraperitoneal (i.p.)…”

Section: Resultsmentioning

confidence: 99%

Neutralization of macrophage migration inhibitory factor improves host survival after Clostridium difficile infection

et al. 2018

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“…; EI Feghaly et al . ). Recent developments in the gut metagenomic studies further intensified the role of dietary components in modifying the gut microbial composition and its clinical correlations (Sekirov et al .…”

Section: Introductionmentioning

confidence: 97%

Prebiotic preferences of human lactobacilli strains in co-culture with bifidobacteria and antimicrobial activity against Clostridium difficile

et al. 2015

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“…B. subtilis and its close relatives are important industrial workhorses, and several Bacillus species are pathogenic to humans. Notably, Firmicutes are one of the two most abundant phyla in the human gut microbiome, and the abundance of several of its members has been repeatedly associated with disease (Arumugam et al, 2011; El Feghaly et al, 2015; Miquel et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Construction and Analysis of Two Genome-Scale Deletion Libraries for Bacillus subtilis

et al. 2017

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SUMMARY A systems level understanding of Gram-positive bacteria is important from both an environmental and health perspective, and is most easily obtained when high-quality, validated genomic resources are available. To this end, we constructed two ordered, barcoded, erythromycin-resistance- and kanamycin-resistance-marked single-gene deletion libraries of the Gram-positive model organism, Bacillus subtilis. The libraries comprise 3968 and 3970 genes, respectively, and overlap in all but four genes. Using these libraries, we update the set of essential genes known for this organism, provide a comprehensive compendium of B. subtilis auxotrophic genes, and identify genes required for utilizing specific carbon and nitrogen sources, as well as those required for growth at low temperature. We report the identification of enzymes catalyzing several missing steps in amino acid biosynthesis. Finally, we describe a suite of high-throughput phenotyping methodologies and apply them to provide a genome-wide analysis of competence and sporulation. Altogether, we provide versatile resources for studying gene function and pathway and network architecture in Gram-positive bacteria.

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The molecular basis of Clostridium difficile disease and host response

Cited by 19 publications

References 52 publications

Neutralization of macrophage migration inhibitory factor improves host survival after Clostridium difficile infection

Neutralization of macrophage migration inhibitory factor improves host survival after Clostridium difficile infection

Prebiotic preferences of human lactobacilli strains in co-culture with bifidobacteria and antimicrobial activity against Clostridium difficile

Construction and Analysis of Two Genome-Scale Deletion Libraries for Bacillus subtilis

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