superoxide reductase mitigates oxygen sensitivity.

causes a serious diarrheal disease and is a common healthcare-associated bacterial pathogen. Although it has a major impact on human health, the mechanistic details of intestinal colonization remain undefined. is highly sensitive to oxygen and requires anaerobic conditions for growth.

Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.

Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis.

Prevalence of diagnostically-discrepant clinical specimens: insights from longitudinal surveillance.

Background: Infection (CDI) is a healthcare-associated diarrheal disease prevalent worldwide. A common diagnostic algorithm relies on a two-step protocol that employs stool enzyme immunoassays (EIAs) to detect the pathogen, and its toxins, respectively. Active CDI is deemed less likely when the Toxin EIA result is negative, even if the pathogen-specific EIA is positive for We recently reported, however, that low-toxin-producing strains recovered from Toxin-negative ('discrepant') clinical stool specimens can be fully pathogenic, and cause lethality in a rodent CDI model.

Heterogeneity in stone culture protocols and endourologist practice patterns: a multi-institutional survey.

Kidney stone cultures can be beneficial in identifying bacteria not detected in urine, yet how stone cultures are performed among endourologists, under what conditions, and by what laboratory methods remain largely unknown. Stone cultures are not addressed by current clinical guidelines. A comprehensive REDCap electronic survey sought responses from directed (n = 20) and listserv elicited (n = 108) endourologists specializing in kidney stone disease.

Enteropathogenic regulates host-cell mitochondrial morphology.

The diarrheagenic pathogen enteropathogenic is responsible for significant childhood mortality and morbidity. EPEC and related attaching-and-effacing (A/E) pathogens use a type III secretion system to hierarchically deliver effector proteins into host cells and manipulate epithelial structure and function. Subversion of host mitochondrial biology is a key aspect of A/E pathogen virulence strategy, but the mechanisms remain poorly defined.

Low-toxin RT027 strains exhibit robust virulence.

is a leading cause of healthcare-associated infections worldwide. Currently, there is a lack of consensus for an optimal diagnostic method for infection (CDI). Multi-step diagnostic algorithms use enzyme immunosorbent analysis (EIA)-based detection of toxins TcdA/TcdB in stool, premised on the rationale that EIA toxin-negative (Tox) patients have less severe disease and shorter diarrhoea duration.

The Alternative Sigma Factor SigL Influences Toxin Production, Sporulation, and Cell Surface Properties.

The alternative sigma factor SigL (Sigma-54) facilitates bacterial adaptation to the extracellular environment by modulating the expression of defined gene subsets. A homolog of the gene encoding SigL is conserved in the diarrheagenic pathogen . To explore the contribution of SigL to biology, we generated -disruption mutants () in strains belonging to two phylogenetically distinct lineages-the human-relevant Ribotype 027 (strain BI-1) and the veterinary-relevant Ribotype 078 (strain CDC1).

Surface-displayed glycopolymers of Clostridioides difficile.

Clostridioides difficile is a leading cause of the healthcare-associated disease C. difficile infection (CDI), which has an annual US burden of over 200 000 cases. CDI mitigation strategies have been complicated by the emergence, and widespread distribution, of phylogenetically diverse lineages, as well as pathogen recalcitrance to genetic manipulation.

Phylogenomic analysis of Clostridioides difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes.

Clostridioides difficile infection (CDI) is a major healthcare-associated diarrheal disease. Consistent with trends across the United States, C. difficile RT106 was the second-most prevalent molecular type in our surveillance in Arizona from 2015 to 2018.

Anti-virulence strategies for infection: advances and roadblocks.

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, (CD), as an Urgent Threat To US healthcare.

Nonsteroidal Anti-inflammatory Drugs Alter the Microbiota and Exacerbate Colitis while Dysregulating the Inflammatory Response.

infection (CDI) is a major public health threat worldwide. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enhanced susceptibility to and severity of CDI; however, the mechanisms driving this phenomenon have not been elucidated. NSAIDs alter prostaglandin (PG) metabolism by inhibiting cyclooxygenase (COX) enzymes.

An Engineered Synthetic Biologic Protects Against Infection.

Morbidity and mortality attributed to infection (CDI) have increased over the past 20 years. Currently, antibiotics are the only US FDA-approved treatment for primary infection, and these are, ironically, associated with disease relapse and the threat of burgeoning drug resistance. We previously showed that non-toxin virulence factors play key roles in CDI, and that colonization factors are critical for disease.

Epithelial maturity influences EPEC-induced desmosomal alterations.

Desmosomes are junctional protein complexes that confer strong adhesive capacity to adjacent host cells. In a recent study, we showed that enteropathogenic Escherichia coli (EPEC) disrupts desmosomes, weakens cell-cell adhesion and perturbs barrier function of intestinal epithelial (C2) cells. Desmosomal damage was dependent on the EPEC effector protein EspH and its inhibitory effect on Rho GTPases.

Enteropathogenic EspH-Mediated Rho GTPase Inhibition Results in Desmosomal Perturbations.

Background & Aims: The diarrheagenic pathogen, enteropathogenic (EPEC), uses a type III secretion system to deliver effector molecules into intestinal epithelial cells (IECs). While exploring the basis for the lateral membrane separation of EPEC-infected IECs, we observed infection-induced loss of the desmosomal cadherin desmoglein-2 (DSG2). We sought to identify the molecule(s) involved in, and delineate the mechanisms and consequences of, EPEC-induced DSG2 loss.

Biofilm Structures in a Mono-Associated Mouse Model of Infection.

infection (CDI) is a major healthcare-associated disease with high recurrence rates. Host colonization is critical for the infectious process, both in first episodes and in recurrent disease, with biofilm formation playing a key role. The ability of to form a biofilm on abiotic surfaces is established, but has not yet been confirmed in the intestinal tract.

A Clostridium difficile Cell Wall Glycopolymer Locus Influences Bacterial Shape, Polysaccharide Production and Virulence.

Clostridium difficile is a diarrheagenic pathogen associated with significant mortality and morbidity. While its glucosylating toxins are primary virulence determinants, there is increasing appreciation of important roles for non-toxin factors in C. difficile pathogenesis.

Characterisation of Clostridium difficile strains isolated from Groote Schuur Hospital, Cape Town, South Africa.

The C. difficile infection rate in South Africa is concerning. Many strains previously isolated from diarrhetic patients at Groote Schuur Hospital were ribotype 017.

The Clostridium difficile Protease Cwp84 Modulates both Biofilm Formation and Cell-Surface Properties.

Clostridium difficile is responsible for 15-20% of antibiotic-associated diarrheas, and nearly all cases of pseudomembranous colitis. Among the cell wall proteins involved in the colonization process, Cwp84 is a protease that cleaves the S-layer protein SlpA into two subunits. A cwp84 mutant was previously shown to be affected for in vitro growth but not in its virulence in a hamster model.

The secreted effector protein EspZ is essential for virulence of rabbit enteropathogenic Escherichia coli.

Attaching and effacing (A/E) pathogens adhere intimately to intestinal enterocytes and efface brush border microvilli. A key virulence strategy of A/E pathogens is the type III secretion system (T3SS)-mediated delivery of effector proteins into host cells. The secreted protein EspZ is postulated to promote enterocyte survival by regulating the T3SS and/or by modulating epithelial signaling pathways.

Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells.

The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) dynamically modulates the survival of infected host intestinal epithelial cells. In the initial stages of infection, several prosurvival signaling events are activated in host cells. These include the phosphorylation of epidermal growth factor receptor (EGFR) and the consequent activation of the phosphatidylinositol-3 kinase/Akt pathway.

Surface-layer protein A (SlpA) is a major contributor to host-cell adherence of Clostridium difficile.

Clostridium difficile is a leading cause of antibiotic-associated diarrhea, and a significant etiologic agent of healthcare-associated infections. The mechanisms of attachment and host colonization of C. difficile are not well defined.

Carbohydrate-based Clostridium difficile vaccines.

Clostridium difficile is responsible for thousands of deaths each year and a vaccine would be welcomed, especially one that would disrupt bacterial maintenance, colonization and persistence in carriers and convalescent patients. Structural explorations at the University of Guelph (ON, Canada) discovered that C. difficile may express three phosphorylated polysaccharides, named PSI, PSII and PSIII; this review captures our recent efforts to create vaccines based on these glycans, especially PSII, the common antigen that has precipitated immediate attention.

Clostridium difficile clinical isolates exhibit variable susceptibility and proteome alterations upon exposure to mammalian cationic antimicrobial peptides.

Clostridium difficile is a leading cause of hospital-acquired bacterial infections in the United States, and the increased incidence of recurrent C. difficile infections is particularly problematic. The molecular mechanisms of C.