Differences in SpeB Protease Activity Among Group A Streptococci Associated with Superficial, Invasive, and Autoimmune Disease

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 May 26

PMID 28545045

Citations 3

Authors

Anhphan T Ly

John P Noto

Odaelys L Walwyn

Robert R Tanz

Stanford T Shulman

William Kabat

Debra E Bessen

Affiliations

Soon will be listed here.

Abstract

The secreted cysteine proteinase SpeB is an important virulence factor of group A streptococci (GAS), whereby SpeB activity varies widely among strains. To establish the degree to which SpeB activity correlates with disease, GAS organisms were recovered from patients with pharyngitis, impetigo, invasive disease or acute rheumatic fever (ARF), and selected for analysis using rigorous sampling criteria; >300 GAS isolates were tested for SpeB activity by casein digestion assays, and each GAS isolate was scored as a SpeB-producer or non-producer. Highly significant statistical differences (p < 0.01) in SpeB production are observed between GAS recovered from patients with ARF (41.5% SpeB-non-producers) compared to pharyngitis (20.5%), invasive disease (16.7%), and impetigo (5.5%). SpeB activity differences between pharyngitis and impetigo isolates are also significant, whereas pharyngitis versus invasive isolates show no significant difference. The disproportionately greater number of SpeB-non-producers among ARF-associated isolates may indicate an altered transcriptional program for many rheumatogenic strains and/or a protective role for SpeB in GAS-triggered autoimmunity.

Citing Articles

Proinflammatory synergy between protease and superantigen streptococcal pyogenic exotoxins.

Johnson A, Bushman S, LaRock D, Diaz J, McCormick J, LaRock C Infect Immun. 2025; 93(3):e0040524.

PMID: 39878494 PMC: 11895496. DOI: 10.1128/iai.00405-24.

Abrin Toxin Paradoxically Increases Protein Synthesis in Stimulated CD4 T-Cells While Decreasing Protein Synthesis in Kidney Cells.

Hernlem B, Rasooly R Curr Issues Mol Biol. 2024; 46(12):13970-13978.

PMID: 39727963 PMC: 11727306. DOI: 10.3390/cimb46120835.

Clinical Snapshot of Group A Streptococcal Isolates from an Australian Tertiary Hospital.

Shaw P, Hayes A, Langton M, Berkhout A, Grimwood K, Davies M Pathogens. 2024; 13(11).

PMID: 39599509 PMC: 11597359. DOI: 10.3390/pathogens13110956.

Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes.

Shumba P, Sura T, Moll K, Chakrakodi B, Tolken L, Hossmann J J Biomed Sci. 2023; 30(1):52.

PMID: 37430325 PMC: 10331992. DOI: 10.1186/s12929-023-00947-x.

Toxins and Superantigens of Group A Streptococci.

Shannon B, McCormick J, Schlievert P Microbiol Spectr. 2019; 7(1).

PMID: 30737912 PMC: 11590448. DOI: 10.1128/microbiolspec.GPP3-0054-2018.

References

Green N, Zhang S, Porcella S, Nagiec M, Barbian K, Beres S . Genome sequence of a serotype M28 strain of group a streptococcus: potential new insights into puerperal sepsis and bacterial disease specificity. J Infect Dis. 2005; 192(5):760-70. DOI: 10.1086/430618. View

Sanderson-Smith M, De Oliveira D, Guglielmini J, McMillan D, Vu T, Holien J . A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis. 2014; 210(8):1325-38. PMC: 6083926. DOI: 10.1093/infdis/jiu260. View

Haukness H, Tanz R, Thomson Jr R, Pierry D, Kaplan E, Beall B . The heterogeneity of endemic community pediatric group a streptococcal pharyngeal isolates and their relationship to invasive isolates. J Infect Dis. 2002; 185(7):915-20. DOI: 10.1086/339407. View

Bessen D, Jones K, Fischetti V . Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever. J Exp Med. 1989; 169(1):269-83. PMC: 2189173. DOI: 10.1084/jem.169.1.269. View

Bessen D, McGregor K, Whatmore A . Relationships between emm and multilocus sequence types within a global collection of Streptococcus pyogenes. BMC Microbiol. 2008; 8:59. PMC: 2359762. DOI: 10.1186/1471-2180-8-59. View

Shulman S, Tanz R, Dale J, Steer A, Smeesters P . Added value of the emm-cluster typing system to analyze group A Streptococcus epidemiology in high-income settings. Clin Infect Dis. 2014; 59(11):1651-2. PMC: 4227576. DOI: 10.1093/cid/ciu649. View

Aziz R, Pabst M, Jeng A, Kansal R, Low D, Nizet V . Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent proteolytic degradation of multiple virulence factors by SpeB. Mol Microbiol. 2003; 51(1):123-34. DOI: 10.1046/j.1365-2958.2003.03797.x. View

Shulman S, Tanz R, Kabat W, Kabat K, Cederlund E, Patel D . Group A streptococcal pharyngitis serotype surveillance in North America, 2000-2002. Clin Infect Dis. 2004; 39(3):325-32. DOI: 10.1086/421949. View

Carapetis J, Steer A, Mulholland E, Weber M . The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005; 5(11):685-94. DOI: 10.1016/S1473-3099(05)70267-X. View

10.

McMillan D, Dreze P, Vu T, Bessen D, Guglielmini J, Steer A . Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study. Clin Microbiol Infect. 2013; 19(5):E222-9. PMC: 4568957. DOI: 10.1111/1469-0691.12134. View

11.

Veasy L, Tani L, Daly J, Korgenski K, Miner L, Bale J . Temporal association of the appearance of mucoid strains of Streptococcus pyogenes with a continuing high incidence of rheumatic fever in Utah. Pediatrics. 2004; 113(3 Pt 1):e168-72. DOI: 10.1542/peds.113.3.e168. View

12.

Nelson D, Garbe J, Collin M . Cysteine proteinase SpeB from Streptococcus pyogenes - a potent modifier of immunologically important host and bacterial proteins. Biol Chem. 2011; 392(12):1077-88. DOI: 10.1515/BC.2011.208. View

13.

Walker M, Hollands A, Sanderson-Smith M, Cole J, Kirk J, Henningham A . DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. Nat Med. 2007; 13(8):981-5. DOI: 10.1038/nm1612. View

14.

Lynskey N, Banerji S, Johnson L, Holder K, Reglinski M, Wing P . Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction. PLoS Pathog. 2015; 11(9):e1005137. PMC: 4564194. DOI: 10.1371/journal.ppat.1005137. View

15.

Bessen D, Sotir C, Readdy T, Hollingshead S . Genetic correlates of throat and skin isolates of group A streptococci. J Infect Dis. 1996; 173(4):896-900. DOI: 10.1093/infdis/173.4.896. View

16.

Bessen D, McShan W, Nguyen S, Shetty A, Agrawal S, Tettelin H . Molecular epidemiology and genomics of group A Streptococcus. Infect Genet Evol. 2014; 33:393-418. PMC: 4416080. DOI: 10.1016/j.meegid.2014.10.011. View

17.

STOLLERMAN G . Rheumatogenic streptococci and autoimmunity. Clin Immunol Immunopathol. 1991; 61(2 Pt 1):131-42. DOI: 10.1016/s0090-1229(05)80019-4. View

18.

Shulman S, Stollerman G, Beall B, Dale J, Tanz R . Temporal changes in streptococcal M protein types and the near-disappearance of acute rheumatic fever in the United States. Clin Infect Dis. 2006; 42(4):441-7. DOI: 10.1086/499812. View

19.

VEASY L, Wiedmeier S, Orsmond G, Ruttenberg H, Boucek M, Roth S . Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med. 1987; 316(8):421-7. DOI: 10.1056/NEJM198702193160801. View

20.

Quinn A, Kosanke S, Fischetti V, Factor S, Cunningham M . Induction of autoimmune valvular heart disease by recombinant streptococcal m protein. Infect Immun. 2001; 69(6):4072-8. PMC: 98471. DOI: 10.1128/IAI.69.6.4072-4078.2001. View