scholarly journals Population Genomics of emm4 Group A Streptococcus Reveals Progressive Replacement with a Hypervirulent Clone in North America

mSystems ◽  
2021 ◽  
Author(s):  
Sruti DebRoy ◽  
Misu Sanson ◽  
Brittany Shah ◽  
Shirjana Regmi ◽  
Luis Alberto Vega ◽  
...  
Keyword(s):  
Population Genomics ◽  
Group A Streptococcus ◽  
Virulence Gene ◽  
Exogenous Dna ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Gene Acquisition ◽  
Invasive Infections ◽  
Group A ◽  
Substantial Morbidity

Severe invasive infections caused by group A Streptococcus (GAS) result in substantial morbidity and mortality in children and adults worldwide. Previously, GAS clonal strain replacement has been attributed to acquisition of exogenous DNA leading to novel virulence gene acquisition or increased virulence gene expression.

scholarly journals Hypervirulent Group AStreptococcusof Genotypeemm3 Invades the Vascular System in Pulmonary Infection of Mice

2018 ◽  
Vol 86 (6) ◽  
Author(s):  
Benfang Lei ◽  
Dylan Minor ◽  
Wenchao Feng ◽  
Mengyao Liu
Keyword(s):  
Pulmonary Infection ◽  
Vascular System ◽  
Regulatory System ◽  
Virulence Gene ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Gram Staining ◽  
Systemic Dissemination ◽  
Group A ◽  
Innate Immune Evasion

ABSTRACTNatural mutations of the two-component regulatory system CovRS are frequently associated with invasive group AStreptococcus(GAS) isolates and lead to the enhancement of virulence gene expression, innate immune evasion, systemic dissemination, and virulence. How CovRS mutations enhance systemic dissemination is not well understood. A hypervirulent GAS isolate of theemm3 genotype, MGAS315, was characterized using a mouse model of pulmonary infection to understand systemic dissemination. This strain has a G1370T mutation in the sensor kinasecovSgene of CovRS. Intratracheal inoculation of MGAS315 led to the lung infection that displayed extensive Gram staining at the alveolar ducts, alveoli, and peribronchovascular and perivascular interstitium. The correction of thecovSmutation did not alter the infection at the alveolar ducts and alveoli but prevented GAS invasion of the peribronchovascular and perivascular interstitium. Furthermore, thecovSmutation allowed MGAS315 to disrupt and degrade the smooth muscle and endothelial layers of the blood vessels, directly contributing to systemic dissemination. It is concluded that hypervirulentemm3 GAScovSmutants can invade the perivascular interstitium and directly attack the vascular system for systemic dissemination.

scholarly journals Identification and Characterization of Serotype-Specific Variation in Group A Streptococcus Pilus Expression

2017 ◽  
Vol 86 (2) ◽  
Author(s):  
Gregory Calfee ◽  
Jessica L. Danger ◽  
Ira Jain ◽  
Eric W. Miller ◽  
Poulomee Sarkar ◽  
...  
Keyword(s):  
Human Blood ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Dependent Manner ◽  
Content Type ◽  
Low Level ◽  
Invasive Infections ◽  
Group A

ABSTRACTIsolates of a given bacterial pathogen often display phenotypic variation, and this can negatively impact public health, for example, by reducing the efficacy of preventative measures. Here, we identify that the human pathogen group AStreptococcus(GAS;Streptococcus pyogenes) expresses pili on its cell surface in a serotype-specific manner. Specifically, we show that serotype M3 GAS isolates, which are nonrandomly associated with causing particularly severe and lethal invasive infections, produce negligible amounts of pili relative to serotype M1 and M49 isolates. Performance of an interserotype transcriptome comparison (serotype M1 versus serotype M3) was instrumental in this discovery. We also identified that the transcriptional regulator Nra positively regulates pilus expression in M3 GAS isolates and that the low level of pilus expression of these isolates correlates with a low level ofnratranscription. Finally, we discovered that the phenotypic consequences of low levels of pilus expression by M3 GAS isolates are a reduced ability to adhere to host cells and an increased ability to survive and proliferate in human blood. We propose that an enhanced ability to survive in human blood, in part due to reduced pilus expression, is a contributing factor in the association of serotype M3 isolates with highly invasive infections. In conclusion, our data show that GAS isolates express pili in a serotype-dependent manner and may inform vaccine development, given that pilus proteins are being discussed as possible GAS vaccine antigens.

scholarly journals Identification of Group A Streptococcus Genes Directly Regulated by CsrRS and Novel Intermediate Regulators

mBio ◽  
2021 ◽  
Author(s):  
Meredith B. Finn ◽  
Kathryn M. Ramsey ◽  
Simon L. Dove ◽  
Michael R. Wessels
Keyword(s):  
Group A Streptococcus ◽  
Human Immune System ◽  
Content Type ◽  
Environmental Signals ◽  
Gas System ◽  
Invasive Infections ◽  
Acquired Heart Disease ◽  
Life Threatening ◽  
Group A ◽  
Human Immune

Group A Streptococcus (GAS) is an important public health threat as a cause of sore throat, skin infections, life-threatening invasive infections, and the postinfectious complications of acute rheumatic fever, a leading cause of acquired heart disease. This work characterizes CsrRS, a GAS system for the detection of environmental signals that enables adaptation of the bacteria for survival in the human throat by regulating the production of products that allow the bacteria to resist clearance by the human immune system.

scholarly journals Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62549 ◽  
Author(s):  
Suzanne J. C. Verhaegh ◽  
Anthony R. Flores ◽  
Alex van Belkum ◽  
James M. Musser ◽  
John P. Hays
Keyword(s):  
Gene Expression ◽  
Moraxella Catarrhalis ◽  
Group A Streptococcus ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Group A

scholarly journals Natural Disruption of Two Regulatory Networks in Serotype M3 Group A Streptococcus Isolates Contributes to the Virulence Factor Profile of This Hypervirulent Serotype

2014 ◽  
Vol 82 (5) ◽  
pp. 1744-1754 ◽  
Author(s):  
Tram N. Cao ◽  
Zhuyun Liu ◽  
Tran H. Cao ◽  
Kathryn J. Pflughoeft ◽  
Jeanette Treviño ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Group A Streptococcus ◽  
Regulatory System ◽  
Mrna Levels ◽  
Bacterial Strains ◽  
Content Type ◽  
Small Regulatory Rna ◽  
Group A

ABSTRACTDespite the public health challenges associated with the emergence of new pathogenic bacterial strains and/or serotypes, there is a dearth of information regarding the molecular mechanisms that drive this variation. Here, we began to address the mechanisms behind serotype-specific variation between serotype M1 and M3 strains of the human pathogenStreptococcus pyogenes(the group AStreptococcus[GAS]). Spatially diverse contemporary clinical serotype M3 isolates were discovered to contain identical inactivating mutations within genes encoding two regulatory systems that control the expression of important virulence factors, including the thrombolytic agent streptokinase, the protease inhibitor-binding protein-G-related α2-macroglobulin-binding (GRAB) protein, and the antiphagocytic hyaluronic acid capsule. Subsequent analysis of a larger collection of isolates determined that M3 GAS, since at least the 1920s, has harbored a 4-bp deletion in thefasCgene of thefasBCAXregulatory system and an inactivating polymorphism in therivRregulator-encoding gene. ThefasCandrivRmutations in M3 isolates directly affect the virulence factor profile of M3 GAS, as evident by a reduction in streptokinase expression and an enhancement of GRAB expression. Complementation of thefasCmutation in M3 GAS significantly enhanced levels of the small regulatory RNA FasX, which in turn enhanced streptokinase expression. Complementation of therivRmutation in M3 GAS restored the regulation ofgrabmRNA abundance but did not alter capsule mRNA levels. While important, thefasCandrivRmutations do not provide a full explanation for why serotype M3 strains are associated with unusually severe invasive infections; thus, further investigation is warranted.

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

scholarly journals SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion

2014 ◽  
Vol 82 (7) ◽  
pp. 2890-2901 ◽  
Author(s):  
Marilena Gallotta ◽  
Giovanni Gancitano ◽  
Giampiero Pietrocola ◽  
Marirosa Mora ◽  
Alfredo Pezzicoli ◽  
...  
Keyword(s):  
Cell Division ◽  
Mammalian Cells ◽  
Group A Streptococcus ◽  
Host Cells ◽  
Knockout Mutant ◽  
Content Type ◽  
Moonlighting Protein ◽  
Group A

ABSTRACTGroup A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of thespy0269gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interactin vitrowith the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cellsin vitroand thatLactococcus lactisexpressing Spy0269 on its cell surface could adhere to mammalian cellsin vitroand to mice nasal mucosain vivo. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (StreptococcuspyogenesAdhesion andDivision protein).

scholarly journals Pathovar Transcriptomes

mSystems ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Amy Platenkamp ◽  
Jay L. Mellies
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Regulatory Networks ◽  
Virulence Gene ◽  
Model System ◽  
Genomic Sequences ◽  
Bacterial Strains ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Link Type

ABSTRACT Archetypal pathogenic bacterial strains are often used to elucidate regulatory networks of an entire pathovar, which encompasses multiple lineages and phylogroups. With enteropathogenic Escherichia coli (EPEC) as a model system, Hazen and colleagues (mSystems 6:e00024-17, 2017, https://doi.org/10.1128/mSystems.00024-17 ) used 9 isolates representing 8 lineages and 3 phylogroups to find that isolates with similar genomic sequences exhibit similarities in global transcriptomes under conditions of growth in medium that induces virulence gene expression, and they found variation among individual isolates. Archetypal pathogenic bacterial strains are often used to elucidate regulatory networks of an entire pathovar, which encompasses multiple lineages and phylogroups. With enteropathogenic Escherichia coli (EPEC) as a model system, Hazen and colleagues (mSystems 6:e00024-17, 2017, https://doi.org/10.1128/mSystems.00024-17 ) used 9 isolates representing 8 lineages and 3 phylogroups to find that isolates with similar genomic sequences exhibit similarities in global transcriptomes under conditions of growth in medium that induces virulence gene expression. They also found variation among individual isolates. Their work illustrates the importance of moving beyond observing regulatory phenomena of a limited number of regulons in a few archetypal strains, with the possibility of correlating clinical symptoms to key transcriptional pathways across lineages and phylogroups.

VicRK and CovR polymorphisms in Streptococcus mutans strains associated with cardiovascular infections

2021 ◽  
Vol 70 (12) ◽  
Author(s):  
Letícia T. Oliveira ◽  
Lívia A. Alves ◽  
Erika N. Harth-Chu ◽  
Ryota Nomura ◽  
Kazuhiko Nakano ◽  
...  
Keyword(s):  
Streptococcus Mutans ◽  
Type Species ◽  
Virulence Gene ◽  
Common Species ◽  
Oral Microbiome ◽  
Nucleotide Polymorphisms ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Coding Regions ◽  
Link Type

Introduction. Streptococcus mutans , a common species of the oral microbiome, expresses virulence genes promoting cariogenic dental biofilms, persistence in the bloodstream and cardiovascular infections. Gap statement. Virulence gene expression is variable among S. mutans strains and controlled by the transcription regulatory systems VicRK and CovR. Aim. This study investigates polymorphisms in the vicRK and covR loci in S. mutans strains isolated from the oral cavity or from the bloodstream, which were shown to differ in expression of covR, vicRK and downstream genes. Methodology. The transcriptional activities of covR, vicR and vicK were compared by RT-qPCR between blood and oral strains after exposure to human serum. PCR-amplified promoter and/or coding regions of covR and vicRK of 18 strains (11 oral and 7 blood) were sequenced and compared to the reference strain UA159. Results. Serum exposure significantly reduced covR and vicR/K transcript levels in most strains (P<0.05), but reductions were higher in oral than in blood strains. Single-nucleotide polymorphisms (SNPs) were detected in covR regulatory and coding regions, but SNPs affecting the CovR effector domain were only present in two blood strains. Although vicR was highly conserved, vicK showed several SNPs, and SNPs affecting VicK regions important for autokinase activity were found in three blood strains. Conclusions. This study reveals transcriptional and structural diversity in covR and vicR/K, and identifies polymorphisms of functional relevance in blood strains, indicating that covR and vicRK might be important loci for S. mutans adaptation to host selective pressures associated with virulence diversity.

Diverse disease processes of group A Streptococcus infection including severe invasive infections among members of a family

2021 ◽  
Vol 14 (4) ◽  
pp. e241339
Author(s):  
Kaori Amari ◽  
Masaki Tago ◽  
Naoko E Katsuki ◽  
Shu-ichi Yamashita
Keyword(s):  
Septic Shock ◽  
Distress Syndrome ◽  
Clinical Course ◽  
Group A Streptococcus ◽  
Bloody Stool ◽  
Laryngeal Oedema ◽  
Invasive Infections ◽  
Group A ◽  
The Right ◽  
Close Contacts

We herein report three cases of group A Streptococcus (GAS) infection in a family. Patient 1, a 50-year-old woman, was transferred to our hospital in shock with acute respiratory distress syndrome, swelling in the right neck and erythemata on both lower extremities. She required intubation because of laryngeal oedema. At the same time, patient 2, a 48-year-old man, was admitted because of septic shock, pneumonia and a pulmonary abscess. Five days later, patient 3, a 91-year-old woman, visited our clinic with bloody stool. All three patients were cured by antibiotics, and GAS was detected by specimen cultures. During these patients’ clinical course, an 84-year-old woman was found dead at home after having been diagnosed with type A influenza. All four patients lived in the same apartment. The GAS genotypes detected in the first three patients were identical. When treating patients with GAS, appropriate management of close contacts is mandatory.

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