Enhanced fermentation of mannitol and release of cytotoxin by Clostridium difficile in alkaline culture media

Kazamias, Michael T.; Sperry, J. F.

doi:10.1128/aem.61.6.2425-2427.1995

Cited by 17 publications

(12 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most carbon sources that repress toxin gene expression are transported inside the bacterium by the phosphoenolpyruvate-dependent carbohydrate: phosphotransferase system (PTS) [ 75 ]. This suggests that the regulation of toxin gene transcription by these rapidly metabolizable carbon sources involves carbon catabolite repression (CCR) [ 19 ].…”

Section: Toxin Expression Is Controlled By the Carbon Catabolite Rmentioning

confidence: 99%

The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

Martin‐Verstraete

Peltier

Dupuy

2016

Toxins

147

142

View full text Add to dashboard Cite

The pathogenic clostridia cause many human and animal diseases, which typically arise as a consequence of the production of potent exotoxins. Among the enterotoxic clostridia, Clostridium difficile is the main causative agent of nosocomial intestinal infections in adults with a compromised gut microbiota caused by antibiotic treatment. The symptoms of C. difficile infection are essentially caused by the production of two exotoxins: TcdA and TcdB. Moreover, for severe forms of disease, the spectrum of diseases caused by C. difficile has also been correlated to the levels of toxins that are produced during host infection. This observation strengthened the idea that the regulation of toxin synthesis is an important part of C. difficile pathogenesis. This review summarizes our current knowledge about the regulators and sigma factors that have been reported to control toxin gene expression in response to several environmental signals and stresses, including the availability of certain carbon sources and amino acids, or to signaling molecules, such as the autoinducing peptides of quorum sensing systems. The overlapping regulation of key metabolic pathways and toxin synthesis strongly suggests that toxin production is a complex response that is triggered by bacteria in response to particular states of nutrient availability during infection.

show abstract

Section: Toxin Expression Is Controlled By the Carbon Catabolite Rmentioning

confidence: 99%

The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

Martin‐Verstraete

Peltier

Dupuy

2016

Toxins

147

142

View full text Add to dashboard Cite

show abstract

“…Genes differentially expressed in LL-37 include loci predicted to encode metabolic pathway components, nutrient acquisition mechanisms, transcriptional regulators, multidrug transporters, antibiotic resistance factors, conjugation-associated proteins, and genes of unknown function. Notably, several of these loci were previously investigated in C. difficile and found to contribute to growth, antimicrobial resistance or virulence, including genes involved in succinate, glucose, fructose, mannitol, ethanolamine, butyrate, acetyl-CoA and amino acid metabolism, oligopeptide permeases, elongation factor (EF-G), ferredoxin oxidoreductase, and ECF sigma factors (13-23).…”

Section: Resultsmentioning

confidence: 99%

TheC. difficile clnRABoperon initiates adaptations to the host environment in response to LL-37

Woods

Edwards

McBride

2018

Preprint

View full text Add to dashboard Cite

1 2 3 4 The C. difficile clnRAB operon initiates adaptations to the host environment in 5 response to LL-37 6 7 24 25 2 26 ABSTRACT27 To cause disease, Clostridioides (Clostridium) difficile must resist killing by innate immune effectors in 28 the intestine, including the host antimicrobial peptide, cathelicidin . The mechanisms that 29 enable C. difficile to adapt to the intestine in the presence of antimicrobial peptides are unknown.30 Expression analyses revealed an operon, CD630_16170-CD630_16190 (clnRAB), which is highly 31 induced by LL-37 and is not expressed in response to other cell-surface active antimicrobials. This 32 operon encodes a predicted transcriptional regulator (clnR) and an ABC transporter system (clnAB), 33 all of which are required for function. Analyses of a clnR mutant indicate that ClnR is a pleiotropic 34 regulator that directly binds to LL-37 and controls expression of numerous genes, including many 35 involved in metabolism, cellular transport, signaling, gene regulation, and pathogenesis. The data 36 suggest that ClnRAB is a novel regulatory mechanism that senses LL-37 as a host signal and 37 regulates gene expression to adapt to the host intestinal environment during infection. 3839 Author Summary 40 C. difficile is a major nosocomial pathogen that causes severe diarrheal disease. Though C. difficile is 41 known to inhabit the human gastrointestinal tract, the mechanisms that allow this pathogen to adapt 42 to the intestine and survive host defenses are not known. In this work, we investigated the response 43 of C. difficile to the host defense peptide, LL-37, to determine the mechanisms underlying host 44 adaptation and survival. Expression analyses revealed a previously unknown locus, which we named 45 clnRAB, that is highly induced by LL-37 and acts as a global regulator of gene expression in C.46 difficile. Mutant analyses indicate that ClnRAB is a novel regulatory system that senses LL-37 as a 47 host signal to regulate adaptation to the intestinal environment. 49Clostridioides difficile (formerly Clostridium difficile) poses a serious, ongoing, public health 50 threat. C. difficile infection (CDI) results in mild to severe diarrhea and leads to approximately 29,000 51 deaths each year in the United States (1). Patients are typically infected after treatment with 52 antibiotics, which disrupt the intestinal microbiota that provide colonization resistance against CDI by 53 competition and release of antimicrobial peptides (AMPs) (1, 2). 54The host innate immune system also plays an important role in the prevention of infections. A 55 critical feature of this defense is the production of AMPs, including defensins, cathelicidin (LL-37), and 56 lysozyme (3, 4). LL-37, a cationic AMP, is of particular importance in CDI because it is not only 57 produced constitutively in the colon by the colonic epithelium, but is also released in high levels from58 neutrophils, which are a key component of the initial immune response to CDI (5). LL-37 is stored in 59 neutrophil granules at a conce...

show abstract

“…Assessment of biosynthesis of the protein toxins ToxA and ToxB in C. difficile cultures was performed by a commercially available ELISA Kit, TOX A/B TEST (TechLab Inc., Blacksburg, VA, USA). For this purpose C. difficile isolates were grown in alkaline trypticase yeast extract medium (pH 8.5) supplemented with 1% mannitol [11] at 37°C for 48 h under anaerobic conditions. Content of ToxA and ToxB was then determined from the supernatants using the TOX A/B TEST following the supplier's instructions.…”

Section: Methodsmentioning

confidence: 99%

Detection of the ADP-ribosyltransferase toxin gene (cdtA) and its activity inClostridium difficileisolates from Equidae

Braun

Herholz

Straub

et al. 2000

FEMS Microbiology Letters

View full text Add to dashboard Cite

Clostridium difficile is an antibiotic-associated emerging pathogen of humans and animals. Thus far three toxins of C. difficile have been described: an enterotoxin (ToxA), a cytotoxin (ToxB) and an ADP-ribosyltransferase (CDT). In the present work we describe the first isolation of CDT producing C. difficile from Equidae with gastro-intestinal disease. Out of 17 C. difficile strains isolated from Equidae, 11 were positive for the genes tcdA and tcdB encoding ToxA and ToxB. In addition four of these 11 isolates were positive for the cdtA gene encoding the catalytic subunit of the ADP-ribosyltransferase CDT. Interestingly none of the isolates derived from canines (41 isolates) and felines (4 isolates) harboured the cdtA gene. In C. difficile field isolates which contained the cdtA gene, ADP-ribosyltransferase activity could also be detected in culture supernatants indicating expression and secretion of CDT. All strains were associated with intestinal disorders, but no association was found for the occurrence of toxins with a specific clinical diagnosis.

show abstract

Enhanced fermentation of mannitol and release of cytotoxin by Clostridium difficile in alkaline culture media

Cited by 17 publications

References 11 publications

The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

The Regulatory Networks That Control Clostridium difficile Toxin Synthesis

TheC. difficile clnRABoperon initiates adaptations to the host environment in response to LL-37

Detection of the ADP-ribosyltransferase toxin gene (cdtA) and its activity inClostridium difficileisolates from Equidae

Contact Info

Product

Resources

About