&lt;b&gt;&lt;i&gt;Streptococcus pyogenes&lt;/i&gt;&lt;/b&gt; Escapes Killing from Extracellular Histones through Plasminogen Binding and Activation by Streptokinase

Nitzsche, Ramona; Köhler, Juliane; Kreikemeyer, Bernd; Oehmcke-Hecht, Sonja

doi:10.1159/000448039

Cited by 18 publications

(17 citation statements)

References 42 publications

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“…GAS infection studies in animals have provided strong evidence that GAS has the ability to manipulate the host fibrinolytic system at many levels [88,89]. On one hand, hijacking the host Plg/Plm on the bacterial surface has provided an energy-efficient strategy to break down the fibrin network during dissemination [55,57,90], and this is achieved with the aid of PAM. Using GAS strains which express both SK2b and PAM genes, it was shown that inactivation of either genes significantly reduces virulence [59].…”

Section: Resultsmentioning

confidence: 99%

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Toward Better Understanding on How Group AStreptococcusManipulates Human Fibrinolytic System

Quek

Whisstock²,

Law

2020

Staphylococcus and Streptococcus

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Group A Streptococcus pyogenes (GAS) is a human pathogen that commonly causes superficial infections such as pharyngitis, but can also lead to systemic and fatal diseases. GAS infection remains to be a major threat in regions with insufficient medical infrastructures, leading to half a million deaths annually worldwide. The pathogenesis of GAS is mediated by a number of virulence factors, which function to facilitate bacterial colonization, immune evasion, and deep tissue invasion. In this review, we will discuss the mechanism of molecular interaction between the host protein and virulence factors that target the fibrinolytic system, including streptokinase (SK), plasminogen-binding group A streptococcal M-like protein (PAM), and streptococcal inhibitor of complement (SIC). We will discuss our current understanding, through structural studies, on how these proteins manipulate the fibrinolytic system during infection.

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Section: Resultsmentioning

confidence: 99%

“…All invasive GAS strains express SK to enhance dissemination [55,56] and colonization within the host [57]. Interestingly, the SK alleles are polymorphic and can be subdivided into two phylogenetic lineages based on the highly variable β domain [38], namely, cluster 1 (SK1) and cluster 2 (SK2) (Figure 4a) [38,58,59].…”

Section: Classification Of Streptokinasementioning

confidence: 99%

Toward Better Understanding on How Group AStreptococcusManipulates Human Fibrinolytic System

Quek

Whisstock²,

Law

2020

Staphylococcus and Streptococcus

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“…S. pyogenes, also known as group A Streptococcus, is a Grampositive bacterium for which the bactericidal action of histones has been previously demonstrated (34,35). Thus, we asked whether soluble FnBPB(163-480) could competitively neutralize the bactericidal activity of H3 for this bacterium.…”

Section: Interactions Of Histones With S Aureus Fnbpbmentioning

confidence: 99%

“…In a study by Nitzsche et al (34), S. pyogenes serotype M49 has been shown to protect itself from histone-killing through PLG acquisition and activation by streptokinase. However, the question was not addressed whether the M49 protein is directly involved in PLG and/or histone binding (34).…”

Section: Interactions Of Histones With S Aureus Fnbpbmentioning

confidence: 99%

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Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Pietrocola

Nobile

Alfeo

et al. 2019

Journal of Biological Chemistry

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Staphylococcus aureus is a Gram-positive bacterium that can cause both superficial and deep-seated infections. Histones released by neutrophils kill bacteria by binding to the bacterial cell surface and causing membrane damage. We postulated that cell wall-anchored proteins protect S. aureus from the bactericidal effects of histones by binding to and sequestering histones away from the cell envelope. Here, we focused on S. aureus strain LAC and by using an array of biochemical assays, including surface plasmon resonance and ELISA, discovered that fibronectin-binding protein B (FnBPB) is the main histone receptor. FnBPB bound all types of histones, but histone H3 displayed the highest affinity and bactericidal activity and was therefore investigated further. H3 bound specifically to the A domain of recombinant FnBPB with a K D of 86 nM, ϳ20-fold lower than that for fibrinogen. Binding apparently occurred by the same mechanism by which FnBPB binds to fibrinogen, because FnBPB variants defective in fibrinogen binding also did not bind H3. An FnBPB-deletion mutant of S. aureus LAC bound less H3 and was more susceptible to its bactericidal activity and to neutrophil extracellular traps, whereas an FnBPBoverexpressing mutant bound more H3 and was more resistant than the WT. FnBPB bound simultaneously to H3 and plasminogen, which after activation by tissue plasminogen activator cleaved the bound histone. We conclude that FnBPB provides a dual immune-evasion function that captures histones and prevents them from reaching the bacterial membrane and simultaneously binds plasminogen, thereby promoting its conversion to plasmin to destroy the bound histone. Staphylococcus aureus is a leading cause of diverse infections ranging from mild skin diseases such as impetigo, cellulitis, and skin abscesses to serious invasive diseases, including sepsis, endocarditis, osteomyelitis, toxic shock syndrome, and necro-tizing pneumoniae (1, 2). Strains that are resistant to multiple antibiotics are a major problem in healthcare settings in developed countries (3). These are referred to as hospital-associated methicillin-resistant S. aureus (MRSA) 3 and occur in individuals with pre-disposing risk factors, such as surgical wounds and indwelling medical devices (4, 5). Recently, there has been a dramatic increase in the incidence of community-associated MRSA infections that occur in otherwise healthy individuals (6, 7). Community-associated MRSA strains, exemplified by the USA300 clone (8), express a low level of resistance to ␤-lactam antibiotics and cause serious skin and soft tissue infections (9-11). S. aureus expresses a plethora of virulence factors, including both secreted and cell wall-anchored (CWA) proteins. The latter mediate adherence to the extracellular matrix, promote invasion of and survival within host cells, neutralize phagocytes, and modulate the immune response (12). CWA proteins are covalently anchored to peptidoglycan via a conserved C-terminal sorting signal mediated by the membrane-associated sortase A (13). Fibronec...

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Pathogenic Mechanisms of Streptococcal Necrotizing Soft Tissue Infections

Siemens

Snäll

Svensson

et al. 2020

Advances in Experimental Medicine and Biology

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<b><i>Streptococcus pyogenes</i></b> Escapes Killing from Extracellular Histones through Plasminogen Binding and Activation by Streptokinase

Cited by 18 publications

References 42 publications

Toward Better Understanding on How Group AStreptococcusManipulates Human Fibrinolytic System

Toward Better Understanding on How Group AStreptococcusManipulates Human Fibrinolytic System

Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Pathogenic Mechanisms of Streptococcal Necrotizing Soft Tissue Infections

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