("Group A Streptococcus"), a Highly Adapted Human Pathogen-Potential Implications of Its Virulence Regulation for Epidemiology and Disease Management

Overview

Journal Pathogens

Date 2021 Jul 2

PMID 34205500

Citations 5

Authors

Nikolai Siemens

Rudolf Lutticken

Affiliations

Soon will be listed here.

Abstract

(group A streptococci; GAS) is an exclusively human pathogen. It causes a variety of suppurative and non-suppurative diseases in people of all ages worldwide. Not all can be successfully treated with antibiotics. A licensed vaccine, in spite of its global importance, is not yet available. GAS express an arsenal of virulence factors responsible for pathological immune reactions. The transcription of all these virulence factors is under the control of three types of virulence-related regulators: (i) two-component systems (TCS), (ii) stand-alone regulators, and (iii) non-coding RNAs. This review summarizes major TCS and stand-alone transcriptional regulatory systems, which are directly associated with virulence control. It is suggested that this treasure of knowledge on the genetics of virulence regulation should be better harnessed for new therapies and prevention methods for GAS infections, thereby changing its global epidemiology for the better.

Citing Articles

The burden of group A (GAS) infections: The challenge continues in the twenty-first century.

Thacharodi A, Hassan S, Vithlani A, Ahmed T, Kavish S, Geli Blacknell N iScience. 2025; 28(1):111677.

PMID: 39877071 PMC: 11773489. DOI: 10.1016/j.isci.2024.111677.

Streptococcus pyogenes carriage rate, associated factors and antimicrobial susceptibility profiles among urban and rural schoolchildren at Gondar city, Northwest Ethiopia.

Gashaw Y, Getaneh A, Kasew D, Tigabie M, Gelaw B Sci Rep. 2025; 15(1):2057.

PMID: 39814816 PMC: 11735781. DOI: 10.1038/s41598-024-82009-2.

Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence.

Deneubourg G, Schiavolin L, Lakhloufi D, Botquin G, Delforge V, Davies M Microorganisms. 2024; 12(11).

PMID: 39597598 PMC: 11596691. DOI: 10.3390/microorganisms12112209.

Incipient empyema as an embolic complication of group A streptococcal septic arthritis in a patient with concomitant influenza B infection.

Callum J, Hinde D, Chew R Respirol Case Rep. 2022; 10(12):e01067.

PMID: 36447458 PMC: 9692190. DOI: 10.1002/rcr2.1067.

Group B Streptococcal Hemolytic Pigment Impairs Platelet Function in a Two-Step Process.

Jahn K, Shumba P, Quach P, Musken M, Wesche J, Greinacher A Cells. 2022; 11(10).

PMID: 35626674 PMC: 9139542. DOI: 10.3390/cells11101637.

References

Carr A, Sledjeski D, Podbielski A, Boyle M, Kreikemeyer B . Similarities between complement-mediated and streptolysin S-mediated hemolysis. J Biol Chem. 2001; 276(45):41790-6. DOI: 10.1074/jbc.M107401200. View

Kuo C, Lin Y, Chuang W, Wu J, Tsao N . Degradation of complement 3 by streptococcal pyrogenic exotoxin B inhibits complement activation and neutrophil opsonophagocytosis. Infect Immun. 2008; 76(3):1163-9. PMC: 2258837. DOI: 10.1128/IAI.01116-07. View

Keyel P, Roth R, Yokoyama W, Heuser J, Salter R . Reduction of streptolysin O (SLO) pore-forming activity enhances inflammasome activation. Toxins (Basel). 2013; 5(6):1105-18. PMC: 3717772. DOI: 10.3390/toxins5061105. View

Heath A, DiRita V, Barg N, Engleberg N . A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B. Infect Immun. 1999; 67(10):5298-305. PMC: 96884. DOI: 10.1128/IAI.67.10.5298-5305.1999. View

Okada N, Liszewski M, Atkinson J, Caparon M . Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc Natl Acad Sci U S A. 1995; 92(7):2489-93. PMC: 42243. DOI: 10.1073/pnas.92.7.2489. View

Podbielski A, Woischnik M, Leonard B, Schmidt K . Characterization of nra, a global negative regulator gene in group A streptococci. Mol Microbiol. 1999; 31(4):1051-64. DOI: 10.1046/j.1365-2958.1999.01241.x. View

Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V . A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues. EMBO J. 2006; 25(19):4628-37. PMC: 1589981. DOI: 10.1038/sj.emboj.7601327. View

Valdes K, Sundar G, Belew A, Islam E, El-Sayed N, Le Breton Y . Glucose Levels Alter the Mga Virulence Regulon in the Group A Streptococcus. Sci Rep. 2018; 8(1):4971. PMC: 5862849. DOI: 10.1038/s41598-018-23366-7. View

Thanert R, Itzek A, Hossmann J, Hamisch D, Madsen M, Hyldegaard O . Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections. Nat Commun. 2019; 10(1):3846. PMC: 6710258. DOI: 10.1038/s41467-019-11722-8. View

10.

Gerlach D, Reichardt W, Vettermann S . Extracellular superoxide dismutase from Streptococcus pyogenes type 12 strain is manganese-dependent. FEMS Microbiol Lett. 1998; 160(2):217-24. DOI: 10.1111/j.1574-6968.1998.tb12914.x. View

11.

Hondorp E, Hou S, Hempstead A, Hause L, Beckett D, McIver K . Characterization of the Group A Streptococcus Mga virulence regulator reveals a role for the C-terminal region in oligomerization and transcriptional activation. Mol Microbiol. 2012; 83(5):953-67. PMC: 3324284. DOI: 10.1111/j.1365-2958.2012.07980.x. View

12.

LaSarre B, Federle M . Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev. 2013; 77(1):73-111. PMC: 3591984. DOI: 10.1128/MMBR.00046-12. View

13.

Beckert S, Kreikemeyer B, Podbielski A . Group A streptococcal rofA gene is involved in the control of several virulence genes and eukaryotic cell attachment and internalization. Infect Immun. 2000; 69(1):534-7. PMC: 97913. DOI: 10.1128/IAI.69.1.534-537.2001. View

14.

Allhorn M, Olsen A, Collin M . EndoS from Streptococcus pyogenes is hydrolyzed by the cysteine proteinase SpeB and requires glutamic acid 235 and tryptophans for IgG glycan-hydrolyzing activity. BMC Microbiol. 2008; 8:3. PMC: 2266755. DOI: 10.1186/1471-2180-8-3. View

15.

VanderWal A, Makthal N, Pinochet-Barros A, Helmann J, Olsen R, Kumaraswami M . Iron Efflux by PmtA Is Critical for Oxidative Stress Resistance and Contributes Significantly to Group A Streptococcus Virulence. Infect Immun. 2017; 85(6). PMC: 5442632. DOI: 10.1128/IAI.00091-17. View

16.

Bessen D, Manoharan A, Luo F, Wertz J, Robinson D . Evolution of transcription regulatory genes is linked to niche specialization in the bacterial pathogen Streptococcus pyogenes. J Bacteriol. 2005; 187(12):4163-72. PMC: 1151717. DOI: 10.1128/JB.187.12.4163-4172.2005. View

17.

Nakata M, Kreikemeyer B . Genetics, Structure, and Function of Group A Streptococcal Pili. Front Microbiol. 2021; 12:616508. PMC: 7900414. DOI: 10.3389/fmicb.2021.616508. View

18.

Ashbaugh C, Wessels M . Absence of a cysteine protease effect on bacterial virulence in two murine models of human invasive group A streptococcal infection. Infect Immun. 2001; 69(11):6683-8. PMC: 100043. DOI: 10.1128/IAI.69.11.6683-6686.2001. View

19.

Kwinn L, Khosravi A, Aziz R, Timmer A, Doran K, Kotb M . Genetic characterization and virulence role of the RALP3/LSA locus upstream of the streptolysin s operon in invasive M1T1 Group A Streptococcus. J Bacteriol. 2006; 189(4):1322-9. PMC: 1797346. DOI: 10.1128/JB.01256-06. View

20.

Xu Y, Ma Y, Sun H . A novel approach to develop anti-virulence agents against group A streptococcus. Virulence. 2012; 3(5):452-3. PMC: 3485984. DOI: 10.4161/viru.21039. View