Streptococcus pyogenes (“Group A Streptococcus”), a Highly Adapted Human Pathogen—Potential Implications of Its Virulence Regulation for Epidemiology and Disease Management

Streptococcus pyogenes (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.

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A Novel Sortase, SrtC2, from Streptococcus pyogenes Anchors a Surface Protein Containing a QVPTGV Motif to the Cell Wall

Journal of Bacteriology ◽

10.1128/jb.186.17.5865-5875.2004 ◽

2004 ◽

Vol 186 (17) ◽

pp. 5865-5875 ◽

Cited By ~ 38

Author(s):

Timothy C. Barnett ◽

Aman R. Patel ◽

June R. Scott

Keyword(s):

Cell Wall ◽

Streptococcus Pyogenes ◽

Group A Streptococcus ◽

Surface Protein ◽

Surface Proteins ◽

Human Pathogen ◽

Hydrophobic Region ◽

C Terminus ◽

Group A ◽

Covalently Linked

ABSTRACT The important human pathogen Streptococcus pyogenes (group A streptococcus GAS), requires several surface proteins to interact with its human host. Many of these are covalently linked by a sortase enzyme to the cell wall via a C-terminal LPXTG motif. This motif is followed by a hydrophobic region and charged C terminus, which are thought to retard the protein in the cell membrane to facilitate recognition by the membrane-localized sortase. Previously, we identified two sortase enzymes in GAS. SrtA is found in all GAS strains and anchors most proteins containing LPXTG, while SrtB is present only in some strains and anchors a subset of LPXTG-containing proteins. We now report the presence of a third sortase in most strains of GAS, SrtC. We show that SrtC mediates attachment of a protein with a QVPTGV motif preceding a hydrophobic region and charged tail. We also demonstrate that the QVPTGV sequence is a substrate for anchoring of this protein by SrtC. Furthermore, replacing this motif with LPSTGE, found in the SrtA-anchored M protein of GAS, leads to SrtA-dependent secretion of the protein but does not lead to its anchoring by SrtA. We conclude that srtC encodes a novel sortase that anchors a protein containing a QVPTGV motif to the surface of GAS.

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Zinc’ing it out: zinc homeostasis mechanisms and their impact on the pathogenesis of human pathogen group A streptococcus

Metallomics ◽

10.1039/c7mt00240h ◽

2017 ◽

Vol 9 (12) ◽

pp. 1693-1702 ◽

Cited By ~ 3

Author(s):

Nishanth Makthal ◽

Muthiah Kumaraswami

Keyword(s):

Streptococcus Pyogenes ◽

Group A Streptococcus ◽

Bacterial Pathogenesis ◽

Zinc Homeostasis ◽

Human Pathogen ◽

Group A

The ability ofStreptococcus pyogenesto resist host-mediated zinc starvation or poisoning is critical for bacterial pathogenesis.

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Antibiotic Treatment, Mechanisms for Failure, and Adjunctive Therapies for Infections by Group A Streptococcus

Frontiers in Microbiology ◽

10.3389/fmicb.2021.760255 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anders F. Johnson ◽

Christopher N. LaRock

Keyword(s):

Streptococcus Pyogenes ◽

Disease Burden ◽

Group A Streptococcus ◽

Human Pathogen ◽

Invasive Infections ◽

Group A ◽

Severe Infections ◽

Treatment Mechanisms ◽

Antibiotic Failure ◽

Global Disease Burden

Group A Streptococcus (GAS; Streptococcus pyogenes) is a nearly ubiquitous human pathogen responsible for a significant global disease burden. No vaccine exists, so antibiotics are essential for effective treatment. Despite a lower incidence of antimicrobial resistance than many pathogens, GAS is still a top 10 cause of death due to infections worldwide. The morbidity and mortality are primarily a consequence of the immune sequelae and invasive infections that are difficult to treat with antibiotics. GAS has remained susceptible to penicillin and other β-lactams, despite their widespread use for 80 years. However, the failure of treatment for invasive infections with penicillin has been consistently reported since the introduction of antibiotics, and strains with reduced susceptibility to β-lactams have emerged. Furthermore, isolates responsible for outbreaks of severe infections are increasingly resistant to other antibiotics of choice, such as clindamycin and macrolides. This review focuses on the challenges in the treatment of GAS infection, the mechanisms that contribute to antibiotic failure, and adjunctive therapeutics. Further understanding of these processes will be necessary for improving the treatment of high-risk GAS infections and surveillance for non-susceptible or resistant isolates. These insights will also help guide treatments against other leading pathogens for which conventional antibiotic strategies are increasingly failing.

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Phage 3396 from a Streptococcus dysgalactiae subsp. equisimilis Pathovar May Have Its Origins in Streptococcus pyogenes

Journal of Bacteriology ◽

10.1128/jb.01590-06 ◽

2007 ◽

Vol 189 (7) ◽

pp. 2646-2652 ◽

Cited By ~ 18

Author(s):

Mark R. Davies ◽

David J. McMillan ◽

Gary H. Van Domselaar ◽

Malcolm K. Jones ◽

Kadaba S. Sriprakash

Keyword(s):

Population Structure ◽

Streptococcus Pyogenes ◽

Group A Streptococcus ◽

Genotypic Diversity ◽

Human Pathogen ◽

Streptococcus Dysgalactiae ◽

Pathogenic Potential ◽

Pathogenic Variants ◽

Group A

ABSTRACT Streptococcus dysgalactiae subsp. equisimilis strains (group G streptococcus [GGS]) are largely defined as commensal organisms, which are closely related to the well-defined human pathogen, the group A streptococcus (GAS). While lateral gene transfers are emerging as a common theme in these species, little is known about the mechanisms and role of these transfers and their effect on the population structure of streptococci in nature. It is now becoming evident that bacteriophages are major contributors to the genotypic diversity of GAS and, consequently, are pivotal to the GAS strain structure. Furthermore, bacteriophages are strongly associated with altering the pathogenic potential of GAS. In contrast, little is know about phages from GGS and their role in the population dynamics of GGS. In this study we report the first complete genome sequence of a GGS phage, Φ3396. Exhibiting high homology to the GAS phage Φ315.1, the chimeric nature of Φ3396 is unraveled to reveal evidence of extensive ongoing genetic diversity and dissemination of streptococcal phages in nature. Furthermore, we expand on our recent findings to identify inducible Φ3396 homologues in GAS from a region of endemicity for GAS and GGS infection. Together, these findings provide new insights into not only the population structure of GGS but also the overall population structure of the streptococcal genus and the emergence of pathogenic variants.

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Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

Terapevt (General Physician) ◽

10.33920/med-12-2003-07 ◽

2020 ◽

pp. 64-70

Author(s):

Anastasiya Laknitskaya

Keyword(s):

Streptococcus Pyogenes ◽

Skin Diseases ◽

Group A Streptococcus ◽

Antibiotic Sensitivity ◽

Antioxidant Defense System ◽

Laboratory Diagnostics ◽

Treatment Methods ◽

Group A ◽

The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

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Genome‐wide analysis of in vivo CcpA binding with and without its key co‐factor HPr in the major human pathogen group A Streptococcus

Molecular Microbiology ◽

10.1111/mmi.14667 ◽

2020 ◽

Author(s):

Sruti DebRoy ◽

Victor Aliaga‐Tobar ◽

Gabriel Galvez ◽

Srishtee Arora ◽

Xiaowen Liang ◽

...

Keyword(s):

Group A Streptococcus ◽

Human Pathogen ◽

Genome Wide Analysis ◽

Genome Wide ◽

Group A

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Association between Resistance to Erythromycin and the Presence of the Fibronectin Binding Protein F1 Gene, prtF1, in Streptococcus pyogenes Isolates from German Pediatric Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.7.2990-2993.2005 ◽

2005 ◽

Vol 49 (7) ◽

pp. 2990-2993 ◽

Cited By ~ 4

Author(s):

Maria Haller ◽

Kirsten Fluegge ◽

Sandra Jasminder Arri ◽

Brit Adams ◽

Reinhard Berner

Keyword(s):

Streptococcus Pyogenes ◽

Pediatric Patients ◽

Group A Streptococcus ◽

Binding Protein ◽

Macrolide Resistance ◽

Group A ◽

Fibronectin Binding Protein ◽

Fibronectin Binding ◽

Cell Invasiveness

ABSTRACT A total of 301 German pediatric group A streptococcus isolates were screened for the presence of macrolide resistance and the fibronectin binding protein F1 gene (prtF1) encoding an adhesin and cell invasiveness protein. The prtF1 gene was present significantly more often among macrolide-resistant isolates. The majority of these were not clonally related.

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Biochemical and biological activity of arginine deiminase from Streptococcus pyogenes M22

Biochemistry and Cell Biology ◽

10.1139/bcb-2015-0069 ◽

2016 ◽

Vol 94 (2) ◽

pp. 129-137 ◽

Cited By ~ 2

Author(s):

Eleonora A. Starikova ◽

Alexey V. Sokolov ◽

Anna Yu. Vlasenko ◽

Larisa A. Burova ◽

Irina S. Freidlin ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Cells ◽

Streptococcus Pyogenes ◽

Group A Streptococcus ◽

Bacterial Pathogen ◽

Arginine Deiminase ◽

Dependent Manner ◽

Group A ◽

Micro Organisms ◽

Dose Dependent

Streptococcus pyogenes (group A Streptococcus; GAS) is an important gram-positive extracellular bacterial pathogen responsible for a number of suppurative infections. This micro-organism has developed complex virulence mechanisms to avoid the host’s defenses. We have previously reported that SDSC from GAS type M22 causes endothelial-cell dysfunction, and inhibits cell adhesion, migration, metabolism, and proliferation in a dose-dependent manner, without affecting cell viability. This work aimed to isolate and characterize a component from GAS type M22 supernatant that suppresses the proliferation of endothelial cells (EA.hy926). In the process of isolating a protein possessing antiproliferative activity we identified arginine deiminase (AD). Further study showed that this enzyme is most active at pH 6.8. Calculating Km and Vmax gave the values of 0.67 mmol·L–1 and 42 s−1, respectively. A distinctive feature of AD purified from GAS type M22 is that its optimum activity and the maximal rate of the catalytic process is close to neutral pH by comparison with enzymes from other micro-organisms. AD from GAS type M22 suppressed the proliferative activity of endothelial cells in a dose-dependent mode. At the same time, in the presence of AD, the proportion of cells in G0/G1 phase increased. When l-Arg was added at increasing concentrations to the culture medium containing AD (3 μg·mL–1), the enzyme’s capacity to inhibit cell proliferation became partially depressed. The proportion of cells in phases S/G2 increased concomitantly, although the cells did not fully recover their proliferation activity. This suggests that AD from GAS type M22 has potential for the suppression of excessive cell proliferation.

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