The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme

Persson, Helena; Vindebro, Reine; Pawel‐Rammingen, Ulrich von

doi:10.1128/iai.00168-13

Cited by 28 publications

(14 citation statements)

References 39 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combined, these data show that Mac/IdeS is expressed at relatively low levels by the WT M1T1 strain but that significant levels of protein are produced as the bacteria undergo the genetic switch, suggesting that Mac/IdeS could play a role in the virulence of the hyperinvasive AP form. As the expression of SpeB, which has been reported to have IgG protease activity in vitro (23–25), is markedly down-regulated in the AP strain (Fig. 1A), the effects of Mac/IdeS on IgG cleavage can be studied independently.…”

Section: Resultsmentioning

confidence: 99%

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Okumura

Anderson

Döhrmann

et al. 2013

mBio

Self Cite

View full text Add to dashboard Cite

The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds.

show abstract

Section: Resultsmentioning

confidence: 99%

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Okumura

Anderson

Döhrmann

et al. 2013

mBio

Self Cite

View full text Add to dashboard Cite

show abstract

“…Certain purified bacterial proteases exhibit direct antibody cleavage activity, such as the V8 protease of S. aureus (99) and the GAS cysteine proteases SpeB (30) and Mac1/IdeS (75). However, detailed mutational and biochemical studies under physiological conditions raise a question as to whether native expression of the latter two proteases is sufficient to impede opsonophagocytosis (91, 95). Gram-positive pathogens can also coopt the activity of a host protease plasminogen to acquire antibody-degrading capacity.…”

Section: Inhibition Of Antibody-mediated Opsonophagocytosismentioning

confidence: 99%

Subterfuge and Sabotage: Evasion of Host Innate Defenses by Invasive Gram-Positive Bacterial Pathogens

Okumura

Nizet

2014

Annu. Rev. Microbiol.

View full text Add to dashboard Cite

The development of a severe invasive bacterial infection in an otherwise healthy individual is one of the most striking and fascinating aspects of human medicine. A small cadre of gram-positive pathogens of the genera Streptococcus and Staphylococcus stand out for their unique invasive disease potential and sophisticated ability to counteract the multifaceted components of human innate defense. This review illustrates how these leading human disease agents evade host complement deposition and activation, impede phagocyte recruitment and activation, resist the microbicidal activities of host antimicrobial peptides and reactive oxygen species, escape neutrophil extracellular traps, and promote and accelerate phagocyte cell death through the action of pore-forming cytolysins. Understanding the molecular basis of bacterial innate immune resistance can open new avenues for therapeutic intervention geared to disabling specific virulence factors and resensitizing the pathogen to host innate immune clearance.

show abstract

“…An important consideration in many reported SpeB studies is the use of purified proteins and nonphysiological conditions. These limitations have been noted in studies demonstrating that SpeB does not cleave immunoglobulins in eukaryotic cell-like conditions, and that the previously observed cleavage activity was unlikely to have functional consequences on September 16, 2020 by guest http://jb.asm.org/ Downloaded from 5 in vivo (23). There has been conflicting evidence regarding the role of SpeB in disease progression and pathogenesis.…”

Section: Introductionmentioning

confidence: 96%

The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human PathogenStaphylococcus aureusUSA300 through Cleavage of the Staphylococcal SdrC Protein

et al. 2020

View full text Add to dashboard Cite

Streptococcus pyogenes, or group A Streptococcus (GAS), is both a pathogen and an asymptomatic colonizer of human hosts and produces a large number of surface-expressed and secreted factors that contribute to a variety of infection outcomes. The GAS-secreted cysteine protease SpeB has been well studied for its effects on the human host; however, despite its broad proteolytic activity, studies on how this factor is utilized in polymicrobial environments are lacking. Here, we utilized various forms of SpeB protease to evaluate its antimicrobial and antibiofilm properties against the clinically important human colonizer Staphylococcus aureus, which occupies niches similar to those of GAS. For our investigation, we used a skin-tropic GAS strain, AP53CovS+, and its isogenic ΔspeB mutant to compare the production and activity of native SpeB protease. We also generated active and inactive forms of recombinant purified SpeB for functional studies. We demonstrate that SpeB exhibits potent biofilm disruption activity at multiple stages of S. aureus biofilm formation. We hypothesized that the surface-expressed adhesin SdrC in S. aureus was cleaved by SpeB, which contributed to the observed biofilm disruption. Indeed, we found that SpeB cleaved recombinant SdrC in vitro and in the context of the full S. aureus biofilm. Our results suggest an understudied role for the broadly proteolytic SpeB as an important factor for GAS colonization and competition with other microorganisms in its niche. IMPORTANCE Streptococcus pyogenes (GAS) causes a range of diseases in humans, ranging from mild to severe, and produces many virulence factors in order to be a successful pathogen. One factor produced by many GAS strains is the protease SpeB, which has been studied for its ability to cleave and degrade human proteins, an important factor in GAS pathogenesis. An understudied aspect of SpeB is the manner in which its broad proteolytic activity affects other microorganisms that co-occupy niches similar to that of GAS. The significance of the research reported herein is the demonstration that SpeB can degrade the biofilms of the human pathogen Staphylococcus aureus, which has important implications for how SpeB may be utilized by GAS to successfully compete in a polymicrobial environment.

show abstract

The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme

Cited by 28 publications

References 39 publications

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Subterfuge and Sabotage: Evasion of Host Innate Defenses by Invasive Gram-Positive Bacterial Pathogens

The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human PathogenStaphylococcus aureusUSA300 through Cleavage of the Staphylococcal SdrC Protein

Contact Info

Product

Resources

About