Regulatory Networks: Linking Toxin Production and Sporulation in Clostridioides difficile
Clostridioides difficile has been recognized as an important nosocomial pathogen that causes diarrheal disease as a consequence of antibiotic exposure and costs the healthcare system billions of dollars every year. C. difficile enters the host gut as dormant spores, germinates into vegetative cells, colonizes the gut, and produces toxins TcdA and/or TcdB, leading to diarrhea and inflammation. Spores are the primary transmission vehicle, while the toxins A and B directly contribute to the disease. Thus, toxin production and sporulation are the key traits that determine the success of C. difficile as a pathogen. Both toxins and spores are produced during the late stationary phase in response to various stimuli. This review provides a comprehensive analysis of the current knowledge on the molecular mechanisms, highlighting the regulatory pathways that interconnect toxin gene expression and sporulation in C. difficile. The roles of carbohydrates, amino acids and other nutrients and signals, in modulating these virulence traits through global regulatory networks are discussed. Understanding the links within the gene regulatory network is crucial for developing effective therapeutic strategies against C. difficile infections, potentially leading to targeted interventions that disrupt the co-regulation of toxin production and sporulation.
Clostridioides difficile toxin B suppresses human neutrophil migration
We investigated the effects of Clostridioides difficile toxin B (TcdB), a major virulence factor in C. difficile infection (CDI), on human neutrophils. TcdB inhibits neutrophil migration via loss of polarity of F-actin polymerization in response to interleukin-8. TcdB facilitates CDI by allowing C. difficile to avert the host immune system.
Butyricimonas paravirosa bacteremia associated with acute terminal ileitis: Case report and literature review
We present the first described case of bacteremia due to Butyricimonas paravirosa, a commensal gram-negative anaerobic bacterium identified by whole-genome sequencing in an elderly patient with acute terminal ileitis, who was successfully treated with ceftriaxone and metronidazole. We reviewed eleven previous cases of infection due to other Butyricimonas spp, which can cause a range of diseases but may be treated conservatively with a short antimicrobial course in the appropriate clinical setting. Additionally, while most Butyricimonas spp are susceptible to empiric anaerobic therapy, drug resistance has been reported in some cases.
Oxygen exposure decreases the yield of high-molecular-weight DNA from some anaerobic bacteria and bacterial communities during DNA extraction
The central challenge in third-generation sequencing lies in meeting the requirements for DNA quality (integrity and purity) and quantity. Therefore, novel improvements in DNA extraction methods are needed to satisfy these requirements. We reasoned that in anaerobic microbial communities, the presence of certain strict anaerobes containing oxygen-activated DNase activity might contribute substantially to the poor integrity of extracted metagenomic DNA (or genomic DNA from some pure cultures) if exposed to air.
Fructo-oligosaccharides promote butyrate production over citrus pectin during in vitro fermentation by colonic inoculum from pig
Fructo-oligosaccharide (FOS) and citrus pectin (CP) are soluble fibers with different chemical composition. However, their fermentation pattern in large intestine remains unclear.
Dogs in Rio de Janeiro as reservoirs of Clostridioides difficile ribotypes causing CDI in humans
In the past decade, the incidence of community-acquired Clostridioides difficile infection (CA-CDI) has increased, suggesting a role for community reservoirs such as animals in its spread.
Serine affects engulfment during the sporulation process in Clostridium perfringens strain SM101
Although Clostridium perfringens sporulation is a key event in the pathogenesis of food-borne illness, the molecules and underlying mechanisms responsible for regulating sporulation are incompletely understood. The present study sought to identify amino acids that affect sporulation in C. perfringens strain SM101.
Changes in the solid-associated bacterial and fungal communities following ruminal in vitro fermentation of winery by-products: aspects of the bioactive compounds and feed safety
Feeding winery by-products (WBP) could affect the bovine microbiome because of their phenol compounds and a transfer of WBP-associated microbiota. This work examined changes in the underexplored solid-associated rumen microbiome following the inclusion of WBP.
Immunogenicity of a pentavalent recombinant Escherichiacoli bacterin against enterotoxemia and botulism in sheep
Producing commercial bacterins/toxoids against Clostridium spp. is laborious and hazardous. Conversely, developing prototype vaccines using purified recombinant toxoids, though safe and effective, is both laborious and costly for application in production animals.
Production of highly soluble and immuno-reactive recombinant flagellin protein of Clostridium chauvoei
Flagellin protein, an integral component of flagella, provides motility to several bacterial species and also acts as a candidate antigen in diagnostics and subunit vaccines. The bulk production of flagellin with retention of all conformational epitopes using recombinant protein technology is of paramount importance in the development of pathogen-specific immuno-assays and vaccines. We describe the production of highly soluble and immuno-reactive rFliA(C) protein of Clostridium chauvoei, a causative agent of blackleg or black quarter (BQ) affecting cattle and small ruminants worldwide. The bacterium is known to possess peritrichous flagella that provide motility and also act as a virulence factor with high protective antigenicity.
Development of two recombinant vaccines against Clostridioides difficile infection and immunogenicity in pregnant sows and neonatal piglets
Clostridioides difficile is the main cause of antibiotic-associated diarrhea in humans and is a major enteropathogen in several animal species. In newborn piglets, colonic lesions caused by C. difficile A and B toxins (TcdA and TcdB, respectively) cause diarrhea and significant production losses.
High value-added chemical production through anaerobic codigestion of corn straw with a microbial consortium, cow manure and cow digestion solution
This study investigated the codigestion of corn straw (CS) with cow manure (CM), cow digestion solution (CD), and a strain consortium (SC) for enhanced volatile fatty acid (VFA) production. The aims of this study were to develop a sustainable technique to increase VFA yields, examine how combining microbial reagents with CS affects VFA production by functional microorganisms, and assess the feasibility of improving microbial diversity through codigestion.
Clinical and microbiological characteristics of anaerobic bacteremia during 1994-2019: A Danish population-based cohort study
Bacteremia with anaerobic bacteria is generally a marker of severe prognosis. However, population-based data is lacking. Our aim was to describe the epidemiology and the 30-day mortality rate of anaerobic bacteremia in a Danish population-based setting.
Clostridium perfringens antigens and challenges for development of vaccines against necrotic enteritis in poultry
Chickens with Necrotic Enteritis (NE), caused by Clostridium perfringens, exhibit acute and chronic symptoms that are difficult to diagnose, leading to significant economic losses. Vaccination is the best method for controlling and preventing NE. However, only two vaccines based on the CPA and NetB toxins have been commercialized, offering partial protection, highlighting the urgent need for more effective vaccines.
Oxygen tolerance in anaerobes as a virulence factor and a health-beneficial property
Oxygen tolerance of anaerobes is a virulence factor, but can also be a beneficial property. Many species have evolved to tolerate or take advantage of the presence of low, especially nanaerobic (≤0.14 %) oxygen concentrations. Oxygen tolerance is genus-, species- and strain-dependent according to their protective mechanisms. It was better expressed in some pathogenic species such as Bacteroides fragilis, Clostridioides difficile, and Clostridium perfringens, as well as in Akkermansia muciniphila than in other potential probiotics such as Alistipes, Blautia and Roseburia spp. Different degrees of oxygen sensitivity were found between the strains of Anaerostipes, Faecalibacterium, and Bifidobacterium spp. Importantly, clostridial spores and anaerobes in biofilms are protected from oxidation. Rubrerythrins and flavodiiron proteins and two regulators (sigma factor B and PerR) contribute to C. difficile protection from reactive oxygen species (ROS). The frequent pathogen, B. fragilis, has numerous protective factors such as enzymes (catalase, superoxide dismutase, alkyl hydroperoxidase, thioredoxin peroxidase, and aerobic-type NrdAB ribonucleotide reductase), and nanaerobic respiration. Seven proteins confer strain-specific oxygen adaptation of Faecalibacterium prausnitzii. Oxygen tolerance protects anaerobes from ROS, shields their DNA and modulates gene expression. Furthermore, oxygen can induce mutations leading to antibiotic resistance as shown in Prevotella melaninogenica. Some Faecalibacterium, Anaerostipes, Bifidobacterium, and Akkermansia strains from the intestinal microbiota exhibiting oxygen tolerance may become next-generation probiotic candidates. Further studies are needed to reveal oxygen effects on more anaerobic species and strains, and the influence of oxygen on antibiotic resistance. More studies on oxygen-tolerant probiotic strains can be useful to optimize biotechnological methods.
Comment on "Antimicrobial susceptibility of Bacteroides fragilis group organisms in Hong Kong, 2020-2021"
Molecular characterization and antibiotic resistance of clinical Bacteroides and related genera from a tertiary care center in Türkiye
This study was conducted to measure the prevalence of antibiotic resistance, and corresponding resistance genes among Bacteroides and related genera in a tertiary hospital.
The identification of Finegoldia dalianensis sp. nov., isolated from the pus of the patient with skin abscess and genomic analysis of the strains belonging to Finegoldia genus
To comprehensively characterize a new species, named Finegoldia dalianensis sp. nov., isolated from the pus of a skin abscess from a patient and genomic analysis of the strains belonging to Finegoldia genus.
A subanalysis of Clostridium perfringens bloodstream infections from a 5-year retrospective nationwide survey (ITANAEROBY)
Clostridium perfingens bloodstream infections (BSIs) can be associated with high mortality rates. We performed a subanalysis of all C. perfringens BSIs enrolled during a multicentric retrospective observational study (ITANAEROBY). Data were collected from January 2016 to December 2020. C. perfringens BSIs were 134 (134/1960, 6.8 %). The highest resistance rate was observed for clindamycin (26/120, 21.6 %), penicillin (11/71, 15.4 %) and metronidazole (14/131, 10.7 %). In conclusion, C. perfringens reduced susceptibility phenotype to first-line therapy.
Growth assessment of mixed cultures of probiotics and common pathogens
In this work, an isothermal microcalorimeter was applied to investigate the antipathogenic activity of three probiotics (Lactobacillus acidophilus, Bifidobacterium lactis and Bifidobacterium bifidum) against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli using the probiotics in mixed culture with the pathogenic microorganisms.