Invasive Group A Streptococcus Research Articles

Reduction in Acute Post-Streptococcal Glomerulonephritis Incidence in Counties Manukau, New Zealand, after the COVID-19 Pandemic.

The COVID-19 pandemic has altered the epidemiology of many common childhood infections, including Group A streptococcal (GAS) disease. Acute post-streptococcal glomerulonephritis (APSGN) is a nonsuppurative complication of GAS pharyngitis and pyoderma. It remains the most common cause of pediatric acute glomerulonephritis globally. In Counties Manukau, New Zealand, APSGN rates have previously been shown to be the highest in the country, with marked ethnic and socioeconomic disparities. We performed a retrospective review of children aged 0-14 years who were discharged from Kidz First Hospital, Counties Manukau, between 2015 and 2023 and met the Strep A Vaccine Global Consortium consensus definition of APSGN. We describe a marked, sustained reduction in APSGN hospitalizations, temporally associated with the COVID-19 pandemic. This ongoing reduction in APSGN incidence is notable in light of contrasting reports of increasing incidence of rheumatic fever in New Zealand and invasive GAS disease internationally.

Presence of Group A streptococcus frequently assayed virulence genes in invasive disease: a systematic review and meta-analysis

IntroductionIt is currently unclear what the role of Group A streptococcus (GAS) virulence factors (VFs) is in contributing to the invasive potential of GAS. This work investigated the evidence for the association of GAS VFs with invasive disease.MethodsWe employed a broad search strategy for studies reporting the presence of GAS VFs in invasive and non-invasive GAS disease. Data were independently extracted by two reviewers, quality assessed, and meta-analyzed using Stata®.ResultsA total of 32 studies reported on 45 putative virulence factors [invasive (n = 3,236); non-invasive (n = 5,218)], characterized by polymerase chain reaction (PCR) (n = 30) and whole-genome sequencing (WGS) (n = 2). The risk of bias was rated as low and moderate, in 23 and 9 studies, respectively. Meta-,analyses of high-quality studies (n = 23) revealed a significant association of speM [OR, 1.64 (95%CI, 1.06; 2.52)] with invasive infection. Meta-analysis of WGS studies demonstrated a significant association of hasA [OR, 1.91 (95%CI, 1.36; 2.67)] and speG [OR, 2.83 (95%CI, 1.63; 4.92)] with invasive GAS (iGAS). Meta-analysis of PCR studies indicated a significant association of speA [OR, 1.59 (95%CI, 1.10; 2.30)] and speK [OR, 2.95 (95%CI, 1.81; 4.80)] with invasive infection. A significant inverse association was observed between prtf1 [OR, 0.42 (95%CI, 0.20; 0.87)] and invasive infection.ConclusionThis systematic review and genomic meta-analysis provides evidence of a statistically significant association with invasive infection for the hasA gene, while smeZ, ssa, pnga3, sda1, sic, and NaDase show statistically significantly inverse associations with invasive infection. SpeA, speK, and speG are associated with GAS virulence; however, it is unclear if they are markers of invasive infection. This work could possibly aid in developing preventative strategies.

Infection route associated with invasive group A streptococcal toxic shock syndrome in maternal deaths: Nationwide analysis of maternal mortalities in Japan

ObjectiveTo clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). MethodsA retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data, and autopsy findings. ResultsAmong the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n=27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020–2023. ConclusionMost antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks, and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.

Complicated pneumonia caused by group A Streptococcus in children - 2022/2023 infectious season outbreak and update on clinical characteristics

BackgroundAn increased incidence of group A Streptococcus (GAS) infections has been observed in pediatric population post-COVID-19 pandemic. While the majority of reports refer to scarlet fever or invasive GAS disease, detailed data on pulmonary manifestations such as complicated community-acquired pneumonia (CAP) are scarce. The aim of this study was to assess the contribution of GAS to complicated CAP in children during the 2022/2023 infectious season. MethodsWe retrospectively analyzed the etiology and clinical presentation of complicated CAP patients hospitalized in our tertiary care center in Warsaw, Poland, between August 2022 and May 2023. ResultsAmong 91 patients with complicated CAP, GAS was the dominant cause constituting 24.2% (22/91; 95% CI 15.8–34.3%) of the study group. 68.2% of GAS pneumonia patients presented symptoms of scarlet fever, and 27.3% had preceding or concurrent viral infection. GAS complicated CAP was associated with longer hospitalization, higher incidence of chest tube insertion, but shorter duration of chest tube drainage than complicated CAP of other etiology. Children with GAS complicated CAP had higher procalcitonin concentration (28.1 vs. 1.5 ng/dL; p<0.0001) and a lower platelets level (254.5 vs. 422 × 103/μL; p = 0.0031) than those with non-GAS infection. ConclusionsGAS is currently the predominant pathogen of complicated CAP in children. Clinicians should be aware of the current epidemiological situation and a more severe course of GAS pneumonia in this age group, and should monitor patients presenting with symptoms of scarlet fever and preceding viral infection closely.

Preadmission course and management of severe pediatric group A streptococcal infections during the 2022-2023 outbreak: a single-center experience.

The massive increase of infections with Group A Streptococcus (GAS) in 2022-2023 coincided in Switzerland with a change of the recommendations for the management of GAS pharyngitis. Therefore, the objective of the present study was to investigate whether the clinical manifestations and management before hospitalization for GAS infection differed in 2022-2023 compared with 2013-2022. Retrospective study of GAS infections requiring hospitalization in patients below 16years. Preadmission illness (modified McIsaac score), oral antibiotic use, and outcome in 2022-2023 were compared with 2013-2022. Time series were compared with surveillance data for respiratory viruses. In 2022-2023, the median modified McIsaac score was lower (2 [IQR 2-3] vs. 3 [IQR 2-4], p = < 0.0001) and the duration of preadmission illness was longer (4days [3-7] vs. 3 [2-6], p = 0.004) than in 2013-2022. In both periods, withholding of preadmission oral antibiotics despite a modified McIsaac score ≥ 3 (12% vs. 18%, n.s.) or ≥ 4 (2.4% vs. 10.0%, p = 0.027) was rare. Respiratory disease, skeletal/muscle infection, and invasive GAS disease were significantly more frequent in 2022-2023, but there were no differences in clinical outcome. The time course of GAS cases in 2022-2023 coincided with the activity of influenza A/B. We found no evidence supporting the hypothesis that the 2022-2023 GAS outbreak was associated with a change in preadmission management possibly induced by the new recommendation for GAS pharyngitis. However, clinical manifestations before admission and comparative examination of time-series strongly suggest that viral co-circulation played an important role in this outbreak.

Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus

Group A Streptococcus (GAS) is a significant human pathogen that poses a global health concern. However, the development of a GAS vaccine has been challenging due to the multitude of diverse M-types and the risk of triggering cross-reactive immune responses. Our previous research has identified a critical role of PrsA1 and PrsA2, surface post-translational molecular chaperone proteins, in maintaining GAS proteome homeostasis and virulence traits. In this study, we aimed to further explore the potential of PrsA1 and PrsA2 as vaccine candidates for preventing GAS infection. We found that PrsA1 and PrsA2 are highly conserved among GAS isolates, demonstrating minimal amino acid variation. Antibodies specifically targeting PrsA1/A2 showed no cross-reactivity with human heart proteins and effectively enhanced neutrophil opsonophagocytic killing of various GAS serotypes. Additionally, passive transfer of PrsA1/A2-specific antibodies conferred protective immunity in infected mice. Compared to alum, immunization with CFA-adjuvanted PrsA1/A2 induced higher levels of Th1-associated IgG isotypes and complement activation and provided approximately 70% protection against invasive GAS challenge. These findings highlight the potential of PrsA1 and PrsA2 as universal vaccine candidates for the development of an effective GAS vaccine.

Polymeric Nanoparticles as Oral and Intranasal Peptide Vaccine Delivery Systems: The Role of Shape and Conjugation.

Mucosal vaccines are highly attractive due to high patient compliance and their suitability for mass immunizations. However, all currently licensed mucosal vaccines are composed of attenuated/inactive whole microbes, which are associated with a variety of safety concerns. In contrast, modern subunit vaccines use minimal pathogenic components (antigens) that are safe but typically poorly immunogenic when delivered via mucosal administration. In this study, we demonstrated the utility of various functional polymer-based nanostructures as vaccine carriers. A Group A Streptococcus (GAS)-derived peptide antigen (PJ8) was selected in light of the recent global spread of invasive GAS infection. The vaccine candidates were prepared by either conjugation or physical mixing of PJ8 with rod-, sphere-, worm-, and tadpole-shaped polymeric nanoparticles. The roles of nanoparticle shape and antigen conjugation in vaccine immunogenicity were demonstrated through the comparison of three distinct immunization pathways (subcutaneous, intranasal, and oral). No additional adjuvant or carrier was required to induce bactericidal immune responses even upon oral vaccine administration.

Group A streptococcal infection in the United Kingdom: an emerging threat

Within group A Streptococcus (GAS), only Streptococcus pyogenes exhibits clinical significance. GAS is typed serologically based on unique surface proteins and critical virulence factors, such as a hyaluronic acid capsule that shields GAS from phagocytosis. The burden of GAS was estimated in the last five years as 14,000 to 25,000 cases of the invasive group A streptococcal disease in the USA with an estimated death from 1,500 to 2,300 cases per year. Early in the summer of 2022 in England, there was more scarlet fever than was anticipated. Early in the current season, the number of notifications rose to unusual heights. The analysis of invasive GAS (iGAS) isolate typing data shows that this season has seen a wide variety of encoding mature M protein (emm) gene sequence types found. Therefore, public health authorities should think about initiatives to increase clinicians’ and the general public’s awareness of GAS infections and to promote their quick diagnosis, molecular testing and antibiotic susceptibility testing, and standard treatment.

Group A Streptococcus Infection in Neonatal Population: A Systematic Review of The Literature.

(1) Background: The importance of group A streptococcus (GAS) infection severity has been recognized in children and adults. However, to our knowledge, there have been no systematic reviews or pooled assessments of the incidence and outcome of invasive GAS (iGAS) disease in neonates, a potentially high-risk population. Therefore, we performed a systematic review of available data regarding the risk factors, clinical presentation, and outcome of GAS infection in neonates. (2) Methods: An electronic search of the existing literature was carried out during the period July 2023-September 2023 in the PubMed and Scopus databases, considering studies referring to GAS infection in the neonatal population. (3) Results: Overall, 39 studies met all the inclusion criteria and were included in this review, evaluating data from 194 neonates. Unfortunately, there were a lot of missing data among the retrieved studies. Our systematic review highlighted the presence of differences with regards to clinical presentation, infection sites, and outcome of GAS invasive disease between neonates with early-onset (EOS) or late-onset sepsis (LOS). Common characteristics of EOS included respiratory distress, rapid deterioration, and high mortality rate irrespective of the infection site, while rash, gastrointestinal tract symptoms, and fever appeared to be the most frequent symptoms/clinical signs and manifestations of LOS disease. The management of severe invasive iGAS disease consists mainly of specific antimicrobial treatment as well as supportive care with fluids and electrolyte supplementation, minimizing or counteracting the effects of toxins. Furthermore, a mortality rate of approximately 14% was recorded for iGAS disease in the total of all studies' neonates. (4) Conclusions: Although iGAS is a rare entity of neonatal infections, the potential severity of the disease and the rapid deterioration requires the development of quick analysis methods for the detection of GAS allowing the prompt diagnosis and administration of the indicated antibiotic treatment. Furthermore, given the exceptional risk for both the pregnant woman and the neonate, it is very important to raise awareness and create easily accessible guidelines that could facilitate the prevention and management of maternal as well as the subsequent neonatal severe iGAS disease.

Group A Streptococcus Primary Peritonitis in Children, New Zealand.

Group A Streptococcus (GAS) primary peritonitis is a rare cause of pediatric acute abdomen (sudden onset of severe abdominal pain); only 26 pediatric cases have been reported in the English language literature since 1980. We discuss 20 additional cases of pediatric primary peritonitis caused by GAS among patients at Starship Children's Hospital, Auckland, New Zealand, during 2010-2022. We compare identified cases of GAS primary peritonitis to cases described in the existing pediatric literature. As rates of rates of invasive GAS increase globally, clinicians should be aware of this cause of unexplained pediatric acute abdomen.

Naturally acquired functional antibody responses to group A Streptococcus differ between major strain types.

Group A Streptococcus (GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain type specific, based on the M-protein (emm-type), the antigenic basis of population-level immunity remains poorly understood. Naturally acquired GAS antibody responses were investigated using intravenous immunoglobulin (IVIG), which contains pooled immunoglobulins from thousands of healthy human donors, as a surrogate for population immunity. Functional opsonophagocytic killing assays were conducted with GAS strains (n = 6) representing the three major emm-pattern types (emm12, A-C pattern; emm53, D-pattern; and emm75, E-pattern). While IVIG induced opsonophagocytic killing of all GAS strains tested, specificity assays showed the profile of protective antibodies differed considerably between emm-types. Antibodies targeting the M-protein were a major component of the functional IVIG antibody response for emm12 and emm53 strains but not for emm75 strains. The striking differences in the contribution of M-protein specific antibodies to killing suggest naturally acquired immunity differs between strains from the major emm-patterns. This challenges the dogma that M-protein is the primary protective antigen across all GAS straintypes. IMPORTANCE Group A Streptococcus (GAS) is a globally important pathogen. With the surge of invasive GAS infections that have occurred in multiple countries, contemporaneous with the relaxation of COVID-19 pandemic restrictions, there is increased interest in the mechanisms underpinning GAS immunity. We utilized intravenous immunoglobulin (IVIG), pooled immunoglobulins from thousands of healthy donors, as a surrogate for population-level immunity to GAS, and explored the contribution of strain-specific (M-type specific) antibodies to GAS immunity using functional killing assays. This revealed striking differences between major strain types as to the contribution of strain specific antibodies to killing. For GAS strains belonging to the E pattern group, M-type specific antibodies do not mediate killing and immunity, which contrasts with strains belonging to pattern A-C and D groups. This challenges the historical dogma, originally proposed by Rebecca Lancefield in the 1950-1960s, that the M-protein is the major protective antigen across all GAS strain types.

Invasive Streptococcus pyogenes: A Short Literature Review

Abstract Objective Streptococcus pyogenes also called Group A streptococci (GAS) is an important pathogen known since past years and infects millions of people around the world every year and can cause death. Although it often causes pharyngitis and skin infections, it can also spread to the bloodstream and cause invasive GAS (iGAS) infections. In this review, studies on the epidemiology of GAS and iGAS and vaccine studies were reviewed. Methods A comprehensive search of databases was conducted up to April 1, 2023 to related studies, in English using the following terms: S. pyogenes, GAS, invasive S. pyogenes infections, iGAS, S. pyogenes vaccine. The data extraction was conducted by two investigators using the same methodology. Results There has been an increase in iGAS infections in various countries in the last year and they have been followed closely. Although the reason for the increase in iGAS cases cannot be determined exactly, it is thought that the recent removal of coronavirus disease 2019 restrictions and the increase in the number of individuals susceptible to GAS and to viral respiratory pathogens is thought to have caused this situation. Another important issue with GAS is the vaccine studies. Vaccines are based on two different targets: M protein-based and non-M protein-based. Phase-I clinical trials have been initiated for some vaccines. Conclusion The increase in recent iGAS infections will draw attention to this agent and accelerate vaccine studies.

Life-Threatening Streptococcal Soft Tissue Infections in Children with Chickenpox: A Post-COVID-19 Case Series

Abstract Objective Children with chickenpox complicated by soft tissue infections can become critically unwell. We investigated cases that were referred to our center to examine the role of medical and surgical management in their care. Methods Children presenting with severe soft tissue infections (SSTIs) associated with varicella infections to a tertiary children's hospital in London serving the South East of England were identified. A retrospective review of the patients' records was performed. Results Ten patients presented having developed severe fever and localized cellulitis at around day 4 of their varicella infection. Group A Streptococcus (GAS) was identified as the causative organism in 90% of cases. Every patient required surgical intervention in addition to medical therapy to establish control of their soft tissue infection. We report 100% survival, and no patients required further reconstructive surgery. Conclusion SSTIs, often caused by invasive GAS, can severely complicate otherwise innocuous cases of chickenpox. Failure to respond to maximal medical therapy should prompt urgent referral to a specialist center, and early surgical intervention can prevent progression to more serious illness.

Identification of distinct impacts of CovS inactivation on the transcriptome of acapsular group A streptococci.

Group A streptococcal (GAS) strains causing severe, invasive infections often have mutations in the control of virulence two-component regulatory system (CovRS) which represses capsule production, and high-level capsule production is considered critical to the GAS hypervirulent phenotype. Additionally, based on studies in emm1 GAS, hyperencapsulation is thought to limit transmission of CovRS-mutated strains by reducing GAS adherence to mucosal surfaces. It has recently been identified that about 30% of invasive GAS strains lacks capsule, but there are limited data regarding the impact of CovS inactivation in such acapsular strains. Using publicly available complete genomes (n = 2,455) of invasive GAS strains, we identified similar rates of CovRS inactivation and limited evidence for transmission of CovRS-mutated isolates for both encapsulated and acapsular emm types. Relative to encapsulated GAS, CovS transcriptomes of the prevalent acapsular emm types emm28, emm87, and emm89 revealed unique impacts such as increased transcript levels of genes in the emm/mga region along with decreased transcript levels of pilus operon-encoding genes and the streptokinase-encoding gene ska. CovS inactivation in emm87 and emm89 strains, but not emm28, increased GAS survival in human blood. Moreover, CovS inactivation in acapsular GAS reduced adherence to host epithelial cells. These data suggest that the hypervirulence induced by CovS inactivation in acapsular GAS follows distinct pathways from the better studied encapsulated strains and that factors other than hyperencapsulation may account for the lack of transmission of CovRS-mutated strains. IMPORTANCE Devastating infections due to group A streptococci (GAS) tend to occur sporadically and are often caused by strains that contain mutations in the control of virulence regulatory system (CovRS). In well-studied emm1 GAS, the increased production of capsule induced by CovRS mutation is considered key to both hypervirulence and limited transmissibility by interfering with proteins that mediate attachment to eukaryotic cells. Herein, we show that the rates of covRS mutations and genetic clustering of CovRS-mutated isolates are independent of capsule status. Moreover, we found that CovS inactivation in multiple acapsular GAS emm types results in dramatically altered transcript levels of a diverse array of cell-surface protein-encoding genes and a unique transcriptome relative to encapsulated GAS. These data provide new insights into how a major human pathogen achieves hypervirulence and indicate that factors other than hyperencapsulation likely account for the sporadic nature of the severe GAS disease.

Parapneumonic effusion in children: Rapid pathogen detection in pleural fluid using multiplex bacterial PCR.

Parapneumonic effusion in children: Rapid pathogen detection in pleural fluid using multiplex bacterial PCR.

Estimating predictors of severity of group A Streptococcus infection in pregnancy

Objective To identify the clinical characteristics of pregnancy associated group A streptococcus (GAS) infection and predictors for intensive care unit (ICU) admission. Methods A retrospective cohort study of culture-proven pregnancy-related GAS infections in tertiary hospital Electronic medical records were reviewed, for cases of cultures positive GAS that were identified between January 2008 and July 2021. A GAS infection was defined by the isolation of the pathogen from a sterile liquid or tissue site. Blood and urine cultures were obtained from all patients with peripartum hyperpyrexia (fever >38 °C). Medical Personnel screening included cultures of the throat, rectum, and skin lesions (if present). In cases of hemodynamic instability patients were transferred ad hoc to ICU, according to the obstetrician and intensivist judgment. Results Of the 143,750 who delivered during the study period, 66 (0.04%) were diagnosed as having a pregnancy associated GAS infection. Of these, 57 patients presented postpartum, and represented the study cohort. The most common presenting signs and symptoms among puerperal GAS, were postpartum pyrexia (72%), abdominal pain (33%), and tachycardia (>100 bpm, 22%). 12 women (21.0%) developed streptococcal toxic shock syndrome (STSS. Predictors for STSS and ICU admission were: antibiotic administration >24 h from presentation postpartum, tachycardia, and a C-reactive protein level >200 mg/L. Women that received antibiotic prophylaxis during labor had a significantly lower rate of STSS (0 vs 10, 22.7%; p = .04). Conclusion Deferral of medical intervention >24 h from the first registered abnormal sign had the most important impact on deterioration of women with invasive puerperal GAS. Antibiotic prophylaxis during labor in women with GAS may reduce associated complications.

Incidence and clinical and microbiological features of invasive and probable invasive streptococcal group A infections in children and adults in the Brussels-Capital Region, 2005–2020

Assess the incidence, risk factors, clinical and microbiological features, and outcome of both probable invasive and invasive group A Streptococcus (GAS) infections in children and adults in the BrusselsCapital Region between 2005 and 2020. A retrospective, multicentric study was performed in three university hospitals in Brussels. Patients were identified through the centralized laboratory information system. Epidemiological and clinical data were collected from patients' hospital records. A total of 467 cases were identified. Incidence has increased from 2.1 to 10.9/100,000 inhabitants between 2009 and 2019 in non-homeless adults while it was above 100/100,000 on homeless in years with available denominators. Most of GAS were isolated from blood (43.6%), and the most common clinical presentation was skin and soft tissue infections (42.8%). A third of all the patients needed surgery, a quarter was admitted to the intensive care unit, and 10% of the adult patients died. Wounds and chickenpox disease were the main risk factors for children. Tobacco, alcohol abuse, wounds or chronic skin lesion, being homeless, and diabetes were identified as major predisposing factors for adults. The most common emm clusters were D4, E4, and AC3; 64% of the isolates were theoretically covered by the 30-valent M-protein vaccine. The burden of invasive and probable invasive GAS infections is on the rise in the studied adult population. We identified potential interventions that could contribute to decrease this burden: appropriate care of wounds, specifically among homeless and patients with risk factors such as diabetes and systematic chickenpox vaccination for children.

Scarlet fever and the dental team

Scarlet fever is a mild, but highly contagious disease caused by Group A Streptococcus (GAS) bacteria. Scarlet fever begins with flu-like symptoms and, within the first 12-48 hours, it is common for a rash to develop that feels like sandpaper to the touch. In rare cases, GAS bacteria can cause an invasive infection that can be fatal. Invasive GAS (iGAS) infection occurs when the bacteria are in a place of the body where they are not normally found, such as the blood stream. Scarlet fever is usually treated with antibiotics, which can reduce the chances of the patient developing iGAS and reduce the risk of them spreading the infection to others. The World Health Organization and UK Health Security Agency have announced that the number of scarlet fever and iGAS cases observed in children has been several times higher than pre-pandemic levels for the equivalent period of time. As healthcare professionals, it is important that the dental team understand key aspects of scarlet fever. Here, scarlet fever symptoms, transmission, clinical manifestations, antibiotic treatment, and risks to the dental team are reviewed. CPD/Clinical Relevance: To describe epidemiology of scarlet fever and discuss the implications for the dental team.

The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus.

ABSTRACTNecrotizing fasciitis is a severe infectious disease that results in significant mortality. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common bacterial pathogens of monomicrobial necrotizing fasciitis. The early diagnosis of necrotizing fasciitis is crucial; however, the typical cutaneous manifestations are not always presented in patients with GAS necrotizing fasciitis, which would lead to miss- or delayed diagnosis. GAS with spontaneous inactivating mutations in the CovR/CovS two-component regulatory system is significantly associated with destructive diseases such as necrotizing fasciitis and toxic shock syndrome; however, no specific marker has been used to identify these invasive clinical isolates. This study evaluated the sensitivity and specificity of using CovR/CovS-controlled phenotypes to identify CovR/CovS-inactivated isolates. Results showed that the increase of hyaluronic acid capsule production and streptolysin O expression were not consistently presented in CovS-inactivated clinical isolates. The repression of SpeB is the phenotype with 100% sensitivity of identifying in CovS-inactivated isolates among 61 clinical isolates. Nonetheless, this phenotype failed to distinguish RopB-inactivated isolates from CovS-inactivated isolates and cannot be utilized to identify CovR-inactivated mutant and RocA (Regulator of Cov)-inactivated isolates. In this study, we identified and verified that PepO, the endopeptidase which regulates SpeB expression through degrading SpeB-inducing quorum-sensing peptide, was a bacterial marker to identify isolates with defects in the CovR/CovS pathway. These results also inform the potential strategy of developing rapid detection methods to identify invasive GAS variants during infection.IMPORTANCE Necrotizing fasciitis is rapidly progressive and life-threatening; if the initial diagnosis is delayed, deep soft tissue infection can progress to massive tissue destruction and toxic shock syndrome. Group A Streptococcus (GAS) with inactivated mutations in the CovR/CovS two-component regulatory system are related to necrotizing fasciitis and toxic shock syndrome; however, no bacterial marker is available to identify these invasive clinical isolates. Inactivation of CovR/CovS resulted in the increased expression of endopeptidase PepO. Our study showed that the upregulation of PepO mediates a decrease in SpeB-inducing peptide (SIP) in the covR mutant, indicating that CovR/CovS modulates SIP-dependent quorum-sensing activity through PepO. Importantly, the sensitivity and specificity of utilizing PepO to identify clinical isolates with defects in the CovR/CovS pathway, including its upstream RocA regulator, were 100%. Our results suggest that identification of invasive GAS by PepO may be a strategy for preventing severe manifestation or poor prognosis after GAS infection.

RARE CASE OF SEVERE NECROTIZING PNEUMONIA DUE TO STREPTOCOCCUS PYOGENES RESULTING IN REFRACTORY HYPOXEMIA

RARE CASE OF SEVERE NECROTIZING PNEUMONIA DUE TO STREPTOCOCCUS PYOGENES RESULTING IN REFRACTORY HYPOXEMIA