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Anales de Pediatria Jun 2020Streptococcus pyogenes (S. pyogenes) is an important human pathogen that is responsible for a broad range of infections, from uncomplicated to more severe and invasive...
INTRODUCTION
Streptococcus pyogenes (S. pyogenes) is an important human pathogen that is responsible for a broad range of infections, from uncomplicated to more severe and invasive diseases with high morbidity/mortality. The M protein (emm type) is a critical virulence factor. Several studies have shown an increased incidence of invasive S. pyogenes disease. This was associated with an increase in the prevalence of M1 and M3 types, well-recognised virulent M types. The aim of the present study was to confirm the resurgence of invasive S. pyogenes disease during 2011-2018 and to identify the relationship between specific M types with disease presentation.
MATERIAL AND METHODS
Isolates were confirmed using standard techniques: colony morphology, β-haemolysis, biochemical tests, and agglutination with specific antisera (DiaMondiaL Strep Kit, DiaMondiaL, Langenhagen, Germany). The antibiotic sensitivity was performed using microdilution (Vitek®2 Compact, bioMeriéux, Inc., Durham, NC). Molecular analysis included the determination of the emm gene and superantigen profile.
RESULTS
A total of 29 invasive isolates were collected (2011-2018) from blood (16), pleural fluid (9), synovial fluid (3), and cerebrospinal fluid (1). One strain per year was isolated between 2011 and 2013, with 2, 5, 4, 6, and 9 strains being isolated between 2014 and 2018, respectively. The most frequent clinical presentations were bacteraemia and pneumonia (10 and 9 cases). The predominant types were M1 (11 isolates) and M3 (3 isolates). A correlation was found between M1 and M3 types, and pneumonia (6/7 cases) and deep soft tissue infections (3/3 cases).
CONCLUSIONS
An increased incidence of invasive S. pyogenes disease was observed during the study period, with M1 and M3 types being those most commonly isolated and associated with pneumonia and deep soft tissue infections.
Topics: Antigens, Bacterial; Bacterial Outer Membrane Proteins; Biomarkers; Carrier Proteins; Child; Child, Preschool; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Retrospective Studies; Severity of Illness Index; Spain; Streptococcal Infections; Streptococcus pyogenes; Virulence Factors
PubMed: 31879253
DOI: 10.1016/j.anpedi.2019.10.014 -
Cell Feb 2014The CRISPR-associated endonuclease Cas9 can be targeted to specific genomic loci by single guide RNAs (sgRNAs). Here, we report the crystal structure of Streptococcus...
The CRISPR-associated endonuclease Cas9 can be targeted to specific genomic loci by single guide RNAs (sgRNAs). Here, we report the crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5 Å resolution. The structure revealed a bilobed architecture composed of target recognition and nuclease lobes, accommodating the sgRNA:DNA heteroduplex in a positively charged groove at their interface. Whereas the recognition lobe is essential for binding sgRNA and DNA, the nuclease lobe contains the HNH and RuvC nuclease domains, which are properly positioned for cleavage of the complementary and noncomplementary strands of the target DNA, respectively. The nuclease lobe also contains a carboxyl-terminal domain responsible for the interaction with the protospacer adjacent motif (PAM). This high-resolution structure and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, thus paving the way for the rational design of new, versatile genome-editing technologies.
Topics: Amino Acid Sequence; Bacteria; CRISPR-Associated Proteins; Crystallography, X-Ray; DNA, Bacterial; Endonucleases; Models, Molecular; Molecular Sequence Data; Protein Structure, Tertiary; RNA, Bacterial; Sequence Alignment; Streptococcus pyogenes; RNA, Small Untranslated
PubMed: 24529477
DOI: 10.1016/j.cell.2014.02.001 -
Nature May 2022Gasdermins (GSDMs) are a family of pore-forming effectors that permeabilize the cell membrane during the cell death program pyroptosis. GSDMs are activated by...
Gasdermins (GSDMs) are a family of pore-forming effectors that permeabilize the cell membrane during the cell death program pyroptosis. GSDMs are activated by proteolytic removal of autoinhibitory carboxy-terminal domains, typically by caspase regulators. However, no activator is known for one member of this family, GSDMA. Here we show that the major human pathogen group A Streptococcus (GAS) secretes a protease virulence factor, SpeB, that induces GSDMA-dependent pyroptosis. SpeB cleavage of GSDMA releases an active amino-terminal fragment that can insert into membranes to form lytic pores. GSDMA is primarily expressed in the skin, and keratinocytes infected with SpeB-expressing GAS die of GSDMA-dependent pyroptosis. Mice have three homologues of human GSDMA, and triple-knockout mice are more susceptible to invasive infection by a pandemic hypervirulent M1T1 clone of GAS. These results indicate that GSDMA is critical in the immune defence against invasive skin infections by GAS. Furthermore, they show that GSDMs can act independently of host regulators as direct sensors of exogenous proteases. As SpeB is essential for tissue invasion and survival within skin cells, these results suggest that GSDMA can act akin to a guard protein that directly detects concerning virulence activities of microorganisms that present a severe infectious threat.
Topics: Animals; Caspases; Keratinocytes; Mice; Pore Forming Cytotoxic Proteins; Pyroptosis; Streptococcus pyogenes; Virulence; Virulence Factors
PubMed: 35545676
DOI: 10.1038/s41586-022-04717-x -
Microbiology Spectrum Mar 2019(group A streptococcus) is remarkable in terms of the large number of diseases it can cause in humans and for the large number of streptococcal factors that have been... (Review)
Review
(group A streptococcus) is remarkable in terms of the large number of diseases it can cause in humans and for the large number of streptococcal factors that have been identified as potential virulence determinants for these diseases. A challenge is to link the function of potential virulence factors to the pathogenesis of specific diseases. An exciting advance has been the development of sophisticated genetic systems for the construction of loss-of-function, conditional, hypomorphic, and gain-of-function mutations in targeted genes that can be used to test specific hypotheses regarding these genes in pathogenesis. This will facilitate a mechanistic understanding of how a specific gene function contributes to the pathogenesis of each streptococcal disease. Since the first genome was completed in 2001, hundreds of complete and draft genome sequences have been deposited. We now know that the average genome is approximately 1.85 Mb and encodes ∼1,800 genes and that the function of most of those genes in pathogenesis remains to be elucidated. However, advances in the development of a variety of genetic tools for manipulation of the genome now provide a platform for the interrogation of gene/phenotype relationships for individual diseases, which may lead to the development of more sophisticated and targeted therapeutic interventions. This article presents an overview of these genetic tools, including the methods of genetic modification and their applications.
Topics: Genes, Bacterial; Genome, Bacterial; Humans; Mutation; Streptococcal Infections; Streptococcus pyogenes; Transduction, Genetic; Transformation, Genetic; Virulence; Virulence Factors
PubMed: 30825299
DOI: 10.1128/microbiolspec.GPP3-0056-2018 -
Frontiers in Cellular and Infection... 2015Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with... (Review)
Review
Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.
Topics: Animals; Bacterial Proteins; Biofilms; Gene Expression Regulation, Bacterial; Humans; Streptococcal Infections; Streptococcus pyogenes
PubMed: 25717441
DOI: 10.3389/fcimb.2015.00015 -
Trends in Microbiology Jul 2017Research on the Gram-positive human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) has long focused on invasive illness, the most severe... (Review)
Review
Research on the Gram-positive human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) has long focused on invasive illness, the most severe manifestations of GAS infection. Recent advances in descriptions of molecular mechanisms of GAS virulence, coupled with massive sequencing efforts to isolate genomes, have allowed the field to better understand the molecular and evolutionary changes leading to pandemic strains. These findings suggest that it is necessary to rethink the dogma involving GAS pathogenesis, and that the most productive avenues for research going forward may be investigations into GAS in its 'normal' habitat, the nasopharynx, and its ability to either live with its host in an asymptomatic lifestyle or as an agent of superficial infections. This review will consider these advances, focusing on the natural history of GAS, the evolution of pandemic strains, and novel roles for several key virulence factors that may allow the field to better understand their physiological role.
Topics: Bacterial Proteins; Evolution, Molecular; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Humans; Mucous Membrane; Serogroup; Streptococcal Infections; Streptococcus pyogenes; Virulence; Virulence Factors
PubMed: 28216292
DOI: 10.1016/j.tim.2017.01.007 -
Frontiers in Cellular and Infection... 2021Bacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate... (Review)
Review
Bacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate phosphotransferase system (PTS) is a conserved pathway in bacteria that couples transport of sugars with phosphorylation to monitor host carbohydrate availability. A family of structurally homologous PTS-regulatory-domain-containing virulence regulators (PCVRs) has been recognized in divergent bacterial pathogens, including Mga and AtxA. These paradigm PCVRs undergo phosphorylation, potentially the PTS, which impacts their dimerization and their activity. Recent work with predicted PCVRs from (Mga) and (MafR) suggest they interact with DNA like nucleoid-associating proteins. Yet, Mga binds to promoter sequences as a homo-dimeric transcription factor, suggesting a bi-modal interaction with DNA. High-resolution crystal structures of 3 PCVRs have validated the domain structure, but also raised additional questions such as how ubiquitous are PCVRs, is PTS-mediated histidine phosphorylation potential PCVRs widespread, do specific sugars signal through PCVRs, and do PCVRs interact with DNA both as transcription factors and nucleoid-associating proteins? Here, we will review known and putative PCVRs based on key domain and functional characteristics and consider their roles as both transcription factors and possibly chromatin-structuring proteins.
Topics: Bacillus anthracis; Bacterial Proteins; Gene Expression Regulation, Bacterial; Streptococcus pyogenes; Virulence
PubMed: 34737980
DOI: 10.3389/fcimb.2021.772874 -
Frontiers in Cellular and Infection... 2019, or Group A Streptococcus (GAS), is a human-restricted pathogen most commonly found in the posterior oropharynx of the human host. The bacterium is responsible for 600... (Review)
Review
, or Group A Streptococcus (GAS), is a human-restricted pathogen most commonly found in the posterior oropharynx of the human host. The bacterium is responsible for 600 million annual cases of pharyngitis globally and has been found to asymptomatically colonize the pharynxes of 4-30% of the population. As such, many studies have utilized animals as models in order to decipher bacterial and host elements that contribute to the bacterial-pharyngeal interaction and determine differences between acute infection and asymptomatic colonization. The aim of this review is to first describe both bacterial and host factors that are important for the pharyngeal persistence of GAS in humans, then to detail the bacterial and host factors that are important for colonization in murine model, and finally to compare the two in order to evaluate the strength of murine pharyngeal colonization as a model for the human-GAS pharyngeal interaction.
Topics: Animals; Carrier State; Disease Models, Animal; Mice; Pharynx; Streptococcal Infections; Streptococcus pyogenes
PubMed: 31119108
DOI: 10.3389/fcimb.2019.00137 -
Scientific Reports Aug 2021Polyols are effective against caries-causing streptococci but the effect on oropharynx-derived pyogenic streptococci is not well characterised. We aimed to study the...
Polyols are effective against caries-causing streptococci but the effect on oropharynx-derived pyogenic streptococci is not well characterised. We aimed to study the effect of erythritol (ERY) and xylitol (XYL) against Streptococcus pyogenes isolated from peritonsillar abscesses (PTA). We used 31 clinical isolates and 5 throat culture collection strains. Inhibition of bacterial growth by polyols at 2.5%, 5% and 10% concentrations was studied and the results were scored. Amylase levels in PTA pus were compared to polyol effectivity scores (PES). Growth curves of four S. pyogenes isolates were analysed. Our study showed that XYL was more effective than ERY inhibiting 71-97% and 48-84% of isolates, respectively, depending of concentrations. 48% of clinical and all throat strains were inhibited by polyols in all concentrations (PES 3). PES was negative or zero in 26% of the isolates in the presence of ERY and in 19% of XYL. ERY enhanced the growth of S. pyogenes isolated from pus with high amylase levels. Polyols in all concentrations inhibited the growth in exponential phase. In conclusion, ERY and XYL are potent growth inhibitors of S. pyogenes isolated from PTA. Therefore, ERY and XYL may have potential in preventing PTA in the patients with frequent tonsillitis episodes.
Topics: Erythritol; Humans; Peritonsillar Abscess; Streptococcal Infections; Streptococcus pyogenes; Sweetening Agents; Vasodilator Agents; Xylitol
PubMed: 34349211
DOI: 10.1038/s41598-021-95367-y -
Microbiology Spectrum May 2024causes a variety of human infections, and hospital outbreaks with this pathogen have also been reported. The purpose of this study is to describe the clinical...
UNLABELLED
causes a variety of human infections, and hospital outbreaks with this pathogen have also been reported. The purpose of this study is to describe the clinical characteristics of an outbreak of involving 15 patients and four healthcare workers (HCWs), as well as the molecular characteristics of the causative isolates. The course and response to the outbreak were reviewed, and information on the characteristics of the patients was extracted retrospectively from the medical records. Whole-genome sequencing of the 16 causative isolates (14 from patients and two from HCWs) was also performed. All 15 patients were postoperative of head and neck cancer with tracheotomy, and 12 had invasive infections, primarily surgical site infections, all of which resolved without causing serious illness. All but the first case was detected more than 7 days after admission. was detected in two patients after empiric antimicrobial administration was performed on all inpatients and HCWs, and the outbreak was finally contained in approximately 2 months. All isolates detected in patients and HCWs belonged to /clade 3, a hypervirulent clone that has emerged worldwide and was classified as sequence type 646. These isolates had single nucleotide polymorphism (SNP) differences of zero to one, indicating clonal transmission. This study demonstrated an outbreak of /clade 3 in a ward of patients with head and neck cancer. The global emergence of hypervirulent isolates may increase the risk of outbreaks among high-risk patients.
IMPORTANCE
This study describes an outbreak of that occurred in a ward caring for patients with head and neck cancer and tracheostomies. Many cases of invasive infections occurred in a short period, and extensive empiric antimicrobial administration on patients and healthcare workers was performed to control the outbreak. Whole-genome sequencing analysis of the causative strains confirmed that it was a monoclonal transmission of strains belonging to /clade 3. The epidemiology and clinical characteristics of infections have changed with the replacement of the prevalent clones worldwide. In the 1980s, there was a reemergence of infections in high-income countries due to the spread of hypervirulent emm1 strains. /clade 3 has recently been spreading worldwide and shares common features with emm1, including increased production of two toxins, NADase, and streptolysin O. The outbreak reported here may reflect the high spreading potential and virulence of /clade 3.
Topics: Humans; Streptococcus pyogenes; Disease Outbreaks; Head and Neck Neoplasms; Streptococcal Infections; Male; Female; Middle Aged; Aged; Cross Infection; Retrospective Studies; Whole Genome Sequencing; Adult; Polymorphism, Single Nucleotide; Surgical Wound Infection; Anti-Bacterial Agents; Aged, 80 and over; Health Personnel
PubMed: 38587390
DOI: 10.1128/spectrum.04260-23