<i>Clostridium septicum</i> Myonecrosis in Congenital Neutropenia

Barnes, Chris; Gerstle, J. Ted; Freedman, Melvin H.; Carção, Manuel

doi:10.1542/peds.2004-0124

Cited by 24 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In atraumatic gas gangrene, infection occurs at distal sites or when there is a breach in the gastrointestinal barrier [ 3 ]. Infection primarily occurs in severely immunocompromised hosts; C. septicum is a major cause of infection in adults with severe hematological malignancies and colorectal cancer, as well as in children with severe neutropenia [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Pore-Forming α-Toxin from Clostridium septicum Activates the MAPK Pathway in a Ras-c-Raf-Dependent and Independent Manner

Chakravorty

Awad

Cheung

et al. 2015

Toxins

View full text Add to dashboard Cite

Clostridium septicum is the causative agent of atraumatic gas gangrene, with α-toxin, an extracellular pore-forming toxin, essential for disease. How C. septicum modulates the host’s innate immune response is poorly defined, although α-toxin-intoxicated muscle cells undergo cellular oncosis, characterised by mitochondrial dysfunction and release of reactive oxygen species. Nonetheless, the signalling events that occur prior to the initiation of oncosis are poorly characterised. Our aims were to characterise the ability of α-toxin to activate the host mitogen activated protein kinase (MAPK) signalling pathway both in vitro and in vivo. Treatment of Vero cells with purified α-toxin activated the extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 arms of the MAPK pathway and stimulated the release of TNF-α in a dose-dependent manner. Studies using inhibitors of all three MAPK components suggested that activation of ERK occurred in a Ras-c-Raf dependent manner, whereas activation of JNK and p38 occurred by a Ras-independent mechanism. Toxin-mediated activation was dependent on efficient receptor binding and pore formation and on an influx of extracellular calcium ions. In the mouse myonecrosis model we showed that the MAPK pathway was activated in tissues of infected mice, implying that it has an important role in the disease process.

show abstract

Section: Introductionmentioning

confidence: 99%

The Pore-Forming α-Toxin from Clostridium septicum Activates the MAPK Pathway in a Ras-c-Raf-Dependent and Independent Manner

Chakravorty

Awad

Cheung

et al. 2015

Toxins

View full text Add to dashboard Cite

show abstract

“…It has been shown that early use of G-CSF may improve the outcome of clostridial infections in neutropenia. 10 Our patient received subcutaneous G-CSF since the day of admission, but exhibited no significant increase in leukocyte count.…”

Section: Discussionmentioning

confidence: 67%

Fulminant Clostridium perfringens sepsis during induction chemotherapy in childhood leukemia

Salvador

Kropshofer

Niederwanger³

et al. 2012

Pediatrics International

View full text Add to dashboard Cite

“…A torsed colonic polyp was found in a recently reported pediatric case of C. septicum infection [18]. Congenital neutropenia and leukemia comprise other conditions in which C. septicum has been described [18,30]. Gastrointestinal pathology in these settings also appears to be the prime site of invasion.…”

Section: Discussionmentioning

confidence: 99%

Clostridium septicum myonecrosis complicating diarrhea-associated hemolytic uremic syndrome

et al. 2008

View full text Add to dashboard Cite

We report the case of a 19-month-old male child with diarrhea-associated hemolytic uremic syndrome (HUS) who developed swelling of the right arm at the site of a peripherally inserted central venous catheter (PICC), fever, and later, ecchymosis. Wound cultures at the time of surgical debridement grew Clostridium septicum. The child subsequently required amputation of the right arm and prolonged therapy with parenteral penicillin and clindamycin. Clostridium septicum infections in children with HUS have been associated with a high rate of mortality. Along with colon cancer, diarrhea-associated HUS comprises a clinical entity which appears to predispose to atraumatic C. septicum infection, where acidic and anaerobic conditions in the diseased colon favor C. septicum invasion. Though not well recognized among pediatric nephrologists, C. septicum infection constitutes a severe, albeit rare, complication of diarrhea-associated HUS, but one in which a high index of suspicion is warranted as aggressive surgical and antibiotic therapy may be life-saving.

show abstract

Clostridium septicum Myonecrosis in Congenital Neutropenia

Cited by 24 publications

References 18 publications

The Pore-Forming α-Toxin from Clostridium septicum Activates the MAPK Pathway in a Ras-c-Raf-Dependent and Independent Manner

The Pore-Forming α-Toxin from Clostridium septicum Activates the MAPK Pathway in a Ras-c-Raf-Dependent and Independent Manner

Fulminant Clostridium perfringens sepsis during induction chemotherapy in childhood leukemia

Clostridium septicum myonecrosis complicating diarrhea-associated hemolytic uremic syndrome

Contact Info

Product

Resources

About