Deficient Skeletal Muscle Regeneration after Injury Induced by a Clostridium perfringens Strain Associated with Gas Gangrene

ABSTRACT Gas gangrene, or clostridial myonecrosis, is usually caused by Clostridium perfringens and may occur spontaneously in association with diabetes mellitus, peripheral vascular disease, or some malignancies but more often after contamination of a deep surgical or traumatic lesion. If not controlled, clostridial myonecrosis results in multiorgan failure, shock, and death, but very little is known about the muscle regeneration process that follows myonecrosis when the infection is controlled. In this study, we characterized the muscle regeneration process after myonecrosis caused in a murine experimental infection with a sublethal inoculum of C. perfringens vegetative cells. The results show that myonecrosis occurs concomitantly with significant vascular injury, which limits the migration of inflammatory cells. A significant increase in cytokines that promote inflammation explains the presence of an inflammatory infiltrate; however, impaired interferon gamma (IFN-γ) expression, a reduced number of M1 macrophages, deficient phagocytic activity, and a prolongation of the permanence of inflammatory cells lead to deficient muscle regeneration. The expression of transforming growth factor β1 (TGF-β1) agrees with the consequent accumulation of collagen in the muscle, i.e., fibrosis observed 30 days after infection. These results provide new information on the pathogenesis of gas gangrene caused by C. perfringens, shed light on the basis of the deficient muscle regenerative activity, and may open new perspectives for the development of novel therapies for patients suffering from this disease.

Clostridium sordelli as a cause of gas gangrene in a trauma patient

Gas gangrene is a necrotic infection of the skin and soft tissue that is associated with high mortality and often necessitating amputation to control the infection. Clostridial myonecrosis is most often cause of gas gangrene and usually present in settings of trauma, surgery, malignancy, and other underlying immunocompromised conditions. The most common causative organism of clostridial myonecrosis is Clostridium perfringens followed by Clostridium septicum. Here, we are reporting an unusual case report of posttraumatic gas gangrene caused by Clostridium sordelli.

Concurrent Host-Pathogen Transcriptional Responses in aClostridium perfringensMurine Myonecrosis Infection

ABSTRACTTo obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murineClostridium perfringensinfection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response toC. perfringensinfection. Comparison of the transcriptome ofC. perfringenscells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change inC. perfringensgene expression. A total of 33% (923) ofC. perfringensgenes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expressionin vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions.IMPORTANCEClostridium perfringensis the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues fromC. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles ofC. perfringenscells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulatedin vivo. These studies have provided a new understanding of the range of factors involved in host-pathogen interactions in a myonecrosis infection.