scholarly journals The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 332 ◽  
Author(s):  
Patience Shumba ◽  
Srikanth Mairpady Shambat ◽  
Nikolai Siemens

Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies.

JCI Insight ◽  
2016 ◽  
Vol 1 (10) ◽  
Author(s):  
Nikolai Siemens ◽  
Bhavya Chakrakodi ◽  
Srikanth Mairpady Shambat ◽  
Marina Morgan ◽  
Helena Bergsten ◽  
...  

2018 ◽  
Vol Volume 11 ◽  
pp. 1959-1974 ◽  
Author(s):  
Hoe Nam Leong ◽  
Asok Kurup ◽  
Mak Yong Tan ◽  
Andrea Lay Hoon Kwa ◽  
Kui Hin Liau ◽  
...  

2016 ◽  
Vol 12 (7) ◽  
pp. e1005732 ◽  
Author(s):  
Karthickeyan Chella Krishnan ◽  
Santhosh Mukundan ◽  
Jeyashree Alagarsamy ◽  
Junguk Hur ◽  
Suba Nookala ◽  
...  

2020 ◽  
Vol 71 (7) ◽  
pp. 1772-1775 ◽  
Author(s):  
Helena Bergsten ◽  
Martin Bruun Madsen ◽  
Francois Bergey ◽  
Ole Hyldegaard ◽  
Steinar Skrede ◽  
...  

Abstract Analyses of plasma collected pre- and postadministration of intravenous immunoglobulin (IVIG) from patients with group A Streptococcus necrotizing soft tissue infections demonstrated a negative correlation between IVIG dose and toxin-triggered T-cell proliferation (r = −.67, P < .0001). One 25-g IVIG dose was sufficient to yield plasma-neutralizing activity against streptococcal superantigens. Clinical Trials Registration. NCT 01790698 and NCT02111161.


2017 ◽  
Vol 42 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Myriam Martinez ◽  
Thomas Peponis ◽  
Aglaia Hage ◽  
Daniel D. Yeh ◽  
Haytham M. A. Kaafarani ◽  
...  

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Asha C Bowen ◽  
Jonathan R Carapetis ◽  
Bart J Currie ◽  
Vance Fowler ◽  
Henry F Chambers ◽  
...  

Abstract Skin and soft tissue infections (SSTI) affect millions of people globally, which represents a significant burden on ambulatory care and hospital settings. The role of sulfamethoxazole-trimethoprim (SXT) in SSTI treatment, particularly when group A Streptococcus (GAS) is involved, is controversial. We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or Staphylococcus aureus, including methicillin-resistant (MRSA). We identified 196 studies, and 15 underwent full text review by 2 reviewers. Observational studies, which mainly focused on SSTI due to S aureus, supported the use of SXT when compared with clindamycin or β-lactams. Of 10 randomized controlled trials, 8 demonstrated the efficacy of SXT for SSTI treatment including conditions involving GAS. These findings support SXT use for treatment of impetigo and purulent cellulitis (without an additional β-lactam agent) and abscess and wound infection. For nonpurulent cellulitis, β-lactams remain the treatment of choice.


2019 ◽  
Author(s):  
Jessica Baude ◽  
Sylvère Bastien ◽  
Yves Gillet ◽  
Pascal Leblanc ◽  
Andreas Itzek ◽  
...  

AbstractNecrotizing Soft Tissue Infections (NSTIs), often reaching the deep fascia and muscle, are mainly caused by group A Streptococcus (GAS) and to a lesser extent by Staphylococcus aureus (SA). Conversely SA is a leading etiologic agent of pyomyositis suggesting that SA could have a specific tropism for the muscle. To assess the pathogenicity of these two bacterial species for muscles cells in comparison to keratinocytes, adhesion and invasion of NSTI-GAS and NSTI-SA were assessed on these cells. Bloodstream infections (BSI) SA isolates and non-invasive coagulase negative Staphylococci (CNS) isolates were used as controls.SA isolates from NSTI and from BSI exhibited stronger internalization into human keratinocytes and myoblasts than CNS or NSTI-GAS. While the median level of SA internalization culminated at 2% in human keratinocytes, it reached over 30% in human myoblasts due to a higher percentage of infected myoblasts (>11%) as compared to keratinocytes (<3%) assessed by transmission electron microscopy. Higher cytotoxicity for myoblasts of NSTI-SA as compared to BSI-SA, was attributed to higher levels of psmα and RNAIII transcripts in NSTI group as compared to hematogenous group. However, the two groups were not discriminated at the genomic level. The cellular basis of high internalization rate in myoblasts was attributed to higher expression of α5β1 integrin in myoblasts as compared to keratinocytes. Major contribution of FnbpAB-integrin α5β1 pathway to internalization was confirmed by isogenic mutants.Our findings suggest the contribution of NSTI-SA severity by its unique propensity to invade and kill myoblasts, a property not shared by NSTI-GAS.ImportanceNecrotizing Soft Tissue Infection (NSTI) is a severe infection caused mainly by group A Streptococcus (GAS) and occasionally by S. aureus (SA); the latter being more often associated with pyomyositis. NSTIs frequently involve the deep fascia and may provoke muscle necrosis. The goal of this study was to determine the tropism and pathogenicity of these two bacterial species for muscle cells. The results revealed a high tropism of SA for myoblasts and myotubes followed by cytotoxicity as opposed to GAS that did not invade these cells. This study uncover a novel mechanism of SA contribution to NSTI with a direct muscle involvement, while in GAS NSTI this is likely indirect, for instance, secondary to vascular occlusion.


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