The Flesh‐Eating Bacterium: What's Next?

Stevens, Dennis L.

doi:10.1086/513851

Cited by 150 publications

(126 citation statements)

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“…5 Epidemiological data also suggest increased incidence and severity of GAS infections in recent years. 2,6,7 Because progression to systemic toxicity and shock can occur throughout a span of hours, early recognition and initiation of aggressive therapies are essential.…”

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confidence: 99%

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Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

Graham

Virtaneva

Porcella

et al. 2006

The American Journal of Pathology

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Molecular mechanisms mediating group A Streptococcus (GAS)-host interactions remain poorly understood but are crucial for diagnostic, therapeutic, and vaccine development. An optimized high-density microarray was used to analyze the transcriptome of GAS during experimental mouse soft tissue infection. The transcriptome of a wild-type serotype M1 GAS strain and an isogenic transcriptional regulator knockout mutant (covR) also were compared. Array datasets were verified by quantitative real-time reverse transcriptase-polymerase chain reaction and in situ immunohistochemistry. The results unambiguously demonstrate that coordinated expression of proven and putative GAS virulence factors is directed toward overwhelming innate host defenses leading to severe cellular damage. We also identified adaptive metabolic responses triggered by nutrient signals and hypoxic/acidic conditions in the host, likely facilitating pathogen persistence and proliferation in soft tissues. Key discoveries included that oxidative stress genes, virulence genes, genes related to amino acid and maltodextrin utilization, and several two-component transcriptional regulators were highly expressed in vivo. This study is the first global analysis of the GAS transcriptome during invasive infection. Coupled with parallel analysis of the covR mutant strain, novel insights have been made into the regulation of GAS virulence in vivo, resulting in new avenues for targeted therapeutic and vaccine research.

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confidence: 99%

“…6,7 Progression to diffuse necrosis of subcutaneous and deep fascia (necrotizing fasciitis) often occurs without overt skin injury 13 and leads to development of vasculitis, intravascular thrombosis, and tissue gangrene. Histopathology of debrided soft tissue reveals acute inflammation of subcutaneous tissue with bacterial aggregates and multifocal necrosis.…”

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confidence: 99%

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

Graham

Virtaneva

Porcella

et al. 2006

The American Journal of Pathology

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“…60 The extent of infection is often not appreciated as the skin findings may be minimal compared with the extent of subcutaneous tissue destruction. 41,58,[61][62][63][64] A delay in diagnosis is common 9 and is associated with increased mortality. 65,66 Severe pain, often of sudden onset and out of proportion to the superficial appearance of the skin, is characteristic of invasive GAS soft tissue infection and should raise this as a diagnostic possibility.…”

Section: History Of Gas Infectionmentioning

confidence: 99%

Severe group a streptococcal infection and streptococcal toxic shock syndrome

Baxter

McChesney

2000

Can J Anesth/J Can Anesth

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Purpose: To review the literature on group A streptococcal toxic shock syndrome, (STSS). Data source: Medline and EMBASE searches were conducted using the key words group A streptococcal toxic shock syndrome, alone and in combination with anesthesia; and septic shock, combined with anesthesia. Medline was also searched using key words intravenous immunoglobulin, (IVIG) and group A streptococcus, (GAS); and group A streptococcus and antibiotic therapy. Other references were included in this review if they addressed the history, microbiology, pathophysiology, incidence, mortality, presentation and management of invasive GAS infections. Relevant references from the papers reviewed were also considered. Articles on the foregoing topics were included regardless of study design. Non-English language studies were excluded. Literature on the efficacy of IVIG and optimal antibiotic therapy was specifically searched. Principal findings: Reports of invasive GAS infections have recently increased. Invasive GAS infection is associated with a toxic shock syndrome, (STSS), in 8 -14% of cases. The STSS characteristically results in shock and multi-organ failure soon after the onset of symptoms, and is associated with a mortality of 33 -81%. Many of these patients will require extensive soft tissue debridement or amputation in the operating room, on an emergency basis. The extent of tissue debridement required is often underestimated before skin incision. Conclusions: Management of STSS requires volume resuscitation, vasopressor/inotrope infusion, antibiotic therapy and supportive care in an intensive care unit, usually including mechanical ventilation. Intravenous immunoglobulin infusion has been recommended. Further studies are needed to define the role of IVIG in STSS management and to determine optimal anesthetic management of patients with septic shock.Objectif: Passer en revue la documentation sur le syndrome de choc toxique streptococcique de groupe A (SCTS). Sources: Des recherches ont été menées dans Medline et EMBASE en utilisant les mots-clés: group A streptococcal toxic shock syndrome, seul et en combinaison avec anesthesia; septic shock, combiné avec anesthesia. Dans Medline, nous avons aussi utilisé les entrées intravenous immunoglobulin (immunoblobuline intraveineuse, IGIV) et group A streptococcus (streptocoque du groupe A, SGA) et antibiotic therapy. Nous avons retenu d'autres références qui concernaient l'histoire, la microbiologie, la physiopathologie, l'incidence, la mortalité, la présenta-tion et le traitement des infections invasives de SGA. Les références pertinentes provenant des articles révisés ont aussi été conservées. Les articles concernant les sujets déjà cités ont été retenus sans tenir compte du type d'é-tude. On a exclu les études d'autres langues que l'anglais. La documentation sur l'efficacité de l'IGIV et sur l'antibiothérapie optimale a été spécialement recherchée. Constatations principales : Les articles sur les infections envahissantes de SGA ont récemment augmenté. L'infection invasive de ...

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“…Consequently, this study focused on examining the impact of mutant residues on protein folding, and subsequent vaccine design, against streptococcal pyrogenic exotoxin A (SPEA) [1]. SPEA 1 is a major virulence factor released by Streptococcus pyogenes and is associated with scarlet fever and severe invasive infections [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%