CodY-Dependent Regulation of Sporulation in Clostridium difficile

Nawrocki, Kathryn L.; Edwards, Adrianne N.; Daou, Nadine; Bouillaut, Laurent; McBride, Shonna M.

doi:10.1128/jb.00220-16

Cited by 74 publications

(115 citation statements)

References 95 publications

(158 reference statements)

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“…Those results (23), obtained using C. difficile codY-null mutants, established that strain variations in the CodY regulation of sporulation can occur even within a clostridial species. Therefore, given the critical role of CodY in C. perfringens type A food poisoning, an isogenic codY-null mutant of SM101, which is a transformable derivative of C. perfringens food-poisoning strain NCTC8798, was generated in the current study (25) to determine whether CodY represses sporulation in this strain as it does in CN3718 (17).…”

Section: Figmentioning

confidence: 71%

“…CodY was first reported to repress sporulation in Bacillus subtilis (24). Recently, the role of CodY in regulating sporulation in Clostridium species has also come under study (17,23). Our group demonstrated that CodY represses sporulation in C. perfringens type D strain CN3718 (17).…”

mentioning

confidence: 76%

“…Interestingly, while disruption of the codY gene increased the level of sporulation in two strains of C. difficile, significant differences in the sporulation frequencies of those two codY-null mutants were noted; i.e., a codY-null mutant of a poorly sporulating strain exhibited a 2-fold increase in sporulation compared to that for its wild-type parent, while a codY-null mutant of a strongly sporulating strain exhibited 1,400-fold more sporulation than its wild-type parent (23).…”

Section: Figmentioning

confidence: 99%

“…Similarly, the McBride group showed that CodY represses sporulation in two Clostridium difficile strains (23). However, the extent of this repression differed significantly between C. difficile strains, indicating that the effects of CodY on gene regulation can vary according to the strain background (23).…”

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confidence: 99%

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CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

Freedman

Evans

et al. 2017

Infect Immun

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Clostridium perfringens type D strains cause enterotoxemia and enteritis in livestock via epsilon toxin production. In type D strain CN3718, CodY was previously shown to increase the level of epsilon toxin production and repress sporulation. C. perfringens type A strains producing C. perfringens enterotoxin (CPE) cause human food poisoning and antibiotic-associated diarrhea. Sporulation is critical for C. perfringens type A food poisoning since spores contribute to transmission and resistance in the harsh food environment and sporulation is essential for CPE production. Therefore, the current study asked whether CodY also regulates sporulation and CPE production in SM101, a derivative of C. perfringens type A food-poisoning strain NCTC8798. An isogenic codY-null mutant of SM101 showed decreased levels of spore formation, along with lower levels of CPE production. A complemented strain recovered wild-type levels of both sporulation and CPE production. When this result was coupled with the earlier results obtained with CN3718, it became apparent that CodY regulation of sporulation varies among different C. perfringens strains. Results from quantitative reverse transcriptase PCR analysis clearly demonstrated that, during sporulation, codY transcript levels remained high in SM101 but rapidly declined in CN3718. In addition, abrB gene expression patterns varied significantly between codY-null mutants of SM101 and CN3718. Compared to the levels in their wild-type parents, the level of abrB gene expression decreased in the CN3718 codYnull mutant strain but significantly increased in the SM101 codY-null mutant strain, demonstrating CodY-dependent regulation differences in abrB expression between these two strains. This difference appears to be important since overexpression of the abrB gene in SM101 reduced the levels of sporulation and enterotoxin production, supporting the involvement of AbrB repression in regulating C. perfringens sporulation.

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Section: Figmentioning

confidence: 71%

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confidence: 76%

Section: Figmentioning

confidence: 99%

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confidence: 99%

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CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

Freedman

Evans

et al. 2017

Infect Immun

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“…Isolates D and E1 also shared an SNV in the oligotransport-ATP binding domain of oppF (Table 4), which belongs to an operon of oligopeptide permease (opp) genes that are involved in regulating sporulation (among other processes) in some species of Bacillus and Clostridium (18,19). In vitro sporulation studies on all isolates revealed no significant difference (data not shown) in the rate of sporulation between isolate D and E1 and all other isolates.…”

Section: Discussionmentioning

confidence: 99%

Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection

et al. 2016

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c Clostridium difficile (Peptoclostridium difficile) is a common health care-associated infection with a disproportionately high incidence in elderly patients. Disease symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. Around 20% of patients may suffer recurrent disease, which often requires rehospitalization of patients. C. difficile was isolated from stool samples from a patient with two recurrent C. difficile infections. PCR ribotyping, whole-genome sequencing, and phenotypic assays were used to characterize these isolates. Genotypic and phenotypic screening of C. difficile isolates revealed multiple PCR ribotypes present and the emergence of rifamycin resistance during the infection cycle. Understanding both the clinical and bacterial factors that contribute to the course of recurrent infection could inform strategies to reduce recurrence. (This study has been registered at ClinicalTrials.gov under registration no. NCT01670149.) C lostridium difficile (Peptoclostridium difficile) is a common health care-associated infection with a disproportionately high incidence in elderly patients. Recurrent Clostridium difficile infection (CDI) is known to occur in approximately 20% of patients following withdrawal of treatment antibiotics (1); however, this may rise to 65% if a patient has a history of CDI (2). Recurring CDI not only causes distress to patients but is also a substantial burden on the health care system due to the increased cost (3) associated with possible prolonged stay or readmission of a patient to the hospital and the readministration of diagnostic tests and antibiotics (4). Collaborations between clinicians and researchers are contributing to knowledge of how both the host and bacterium are affecting recurrent disease in order to reduce recurrence rates through personalized patient care regimens (5).In this study, multiple stool samples from a patient enrolled in a clinical trial were collected and C. difficile was isolated. The strains isolated from these samples were then phenotypically and genotypically characterized to deduce if changes in the C. difficile strain genotype and phenotype could have contributed to recurrent infection.Case. A male participant (01008), aged 85 years, had a history of chronic kidney disease and was on multiple long-term medications, including bumetanide, candesartan, digoxin, simvastatin, doxazosin, ferrous fumarate, and prednisolone. Three months prior to trial enrollment the participant received cefuroxime and gentamicin for a urinary tract infection. One month prior to trial enrollment he was admitted to the hospital, where he received clindamycin (both orally and intravenously) for an infected leg ulcer.In June 2013, after being readmitted to the hospital, he was diagnosed with CDI (Table 1, sample A), treated with metronidazole (MET), and discharged. He was diagnosed again with CDI in July (Table 1, sample B) and was treated again with MET.In July 2013, within 5 days of cessation of successful treatment of CDI with MET (defined as ce...

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Genomic insights into clostridia in bioenergy production: Comparison of metabolic capabilities and evolutionary relationships

Kumar,

Barbora,

Moholkar

2023

Biotech & Bioengineering

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Bacteria from diverse genera, including Acetivibrio, Bacillus, Cellulosilyticum, Clostridium, Desulfotomaculum, Lachnoclostridium, Moorella, Ruminiclostridium, and Thermoanaerobacterium, have attracted significant attention due to their versatile metabolic capabilities encompassing acetogenic, cellulolytic, and C1‐metabolic properties, and acetone‐butanol‐ethanol fermentation. Despite their biotechnological significance, a comprehensive understanding of clostridial physiology and evolution has remained elusive. This study reports an extensive comparative genomic analysis of 48 fully sequenced bacterial genomes from these genera. Our investigation, encompassing pan‐genomic analysis, central carbon metabolism comparison, exploration of general genome features, and in‐depth scrutiny of Cluster of Orthologous Groups genes, has established a holistic whole‐genome‐based phylogenetic framework. We have classified these strains into acetogenic, butanol‐producing, cellulolytic, CO2‐fixating, chemo(litho/organo)trophic, and heterotrophic categories, often exhibiting overlaps. Key outcomes include the identification of misclassified species and the revelation of insights into metabolic features, energy conservation, substrate utilization, stress responses, and regulatory mechanisms. These findings can provide guidance for the development of efficient microbial systems for sustainable bioenergy production. Furthermore, by addressing fundamental questions regarding genetic relationships, conserved genomic features, pivotal enzymes, and essential genes, this study has also contributed to our comprehension of clostridial biology, evolution, and their shared metabolic potential.

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CodY-Dependent Regulation of Sporulation in Clostridium difficile

Cited by 74 publications

References 95 publications

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection

Genomic insights into clostridia in bioenergy production: Comparison of metabolic capabilities and evolutionary relationships

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