Clostridium difficile
Research Article | Host-Microbe BiologyThe Initial Gut Microbiota and Response to Antibiotic Perturbation Influence Clostridioides difficile Clearance in MiceClostridioides difficile is a leading nosocomial infection. Although perturbation to the gut microbiota is an established risk, there is variation in who becomes asymptomatically colonized, develops an infection, or has adverse infection outcomes. Mouse models of C. difficile infection (CDI) are...
Research Article | Molecular Biology and PhysiologyRedefining the Clostridioides difficile σB Regulon: σB Activates Genes Involved in Detoxifying Radicals That Can Result from the Exposure to Antimicrobials and Hydrogen PeroxideSigma B is the alternative sigma factor governing stress response in many Gram-positive bacteria. In C. difficile, a sigB mutant shows pleiotropic transcriptional effects. Here, we determine genes that are likely direct targets of σB by evaluating the transcriptional effects of σB overproduction, provide biochemical evidence of direct...
Research Article | Molecular Biology and PhysiologyArchitecture and Self-Assembly of Clostridium sporogenes and Clostridium botulinum Spore Surfaces Illustrate a General Protective Strategy across Spore FormersBacteria such as those causing botulism and anthrax survive harsh conditions and spread disease as spores. Distantly related species have similar spore architectures with protective proteinaceous layers aiding adhesion and targeting. The structures that confer these common properties are largely unstudied, and the proteins involved can be very dissimilar in sequence. We identify CsxA as a cysteine-rich protein that self-assembles in a...
Research Article | Host-Microbe BiologyGenetic Association Reveals Protection against Recurrence of Clostridium difficile Infection with Bezlotoxumab TreatmentClostridium difficile infection is associated with significant clinical morbidity and mortality; antibacterial treatments are effective, but recurrence of C. difficile infection is common. In this genome-wide association study, we explored whether host genetic variability affected treatment...
Research Article | Host-Microbe BiologyZupT Facilitates Clostridioides difficile Resistance to Host-Mediated Nutritional ImmunityDuring infection, pathogenic organisms must acquire essential transition metals from the host environment. Through the process of nutritional immunity, the host employs numerous strategies to restrict these key nutrients from invading pathogens. In this study, we describe a mechanism by which the important human pathogen Clostridioides difficile resists transition-...
Observation | Host-Microbe BiologyThe Proton Pump Inhibitor Omeprazole Does Not Promote Clostridioides difficile Colonization in a Murine ModelAntibiotics are the primary risk factor for Clostridioides difficile infections (CDIs), but other factors may also increase a person’s risk. In epidemiological studies, proton pump inhibitor (PPI) use has been associated with CDI incidence and recurrence. PPIs have also been associated with alterations in the human intestinal microbiota in observational and...
Research Article | Clinical Science and EpidemiologyOutbreak of Murine Infection with Clostridium difficile Associated with the Administration of a Pre- and Perinatal Methyl Donor DietClostridium difficile infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also...
Research Article | Host-Microbe BiologyThe Gut Microbiota Is Associated with Clearance of Clostridium difficile Infection Independent of Adaptive ImmunityClostridium difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a...
Research Article | Host-Microbe BiologyCyclic Diguanylate Regulates Virulence Factor Genes via Multiple Riboswitches in Clostridium difficileIn Clostridium difficile, the signaling molecule c-di-GMP regulates multiple processes affecting its ability to cause disease, including swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we used RNA-seq to define the transcriptional regulon of c-di-GMP in...
Research Article | Host-Microbe BiologyGerminant Synergy Facilitates Clostridium difficile Spore Germination under Physiological ConditionsClostridium difficile is an anaerobic spore-forming human pathogen that is the leading cause of nosocomial infectious diarrhea worldwide. Germination of infectious spores is the first step in the development of a C. difficile infection (CDI) after ingestion and passage through the stomach. This...