A rapid molecular detection tool for toxigenic M1UK Streptococcus pyogenes.

BACKGROUND: The gradual replacement of the Streptococcus pyogenes M1global genotype by a newly emergent M1UK variant is a global public health threat warranting increased surveillance. M1UK differs from progenitor M1global genotype by 27 single nucleotide polymorphisms (SNPs) and is characterised by increased speA superantigen expression in vitro. METHODS: An allele-specific real-time PCR assay was developed for the rapid detection of M1UK strains. The assay was used in combination with whole-genome sequencing to determine emm (sub)type distribution for 51 invasive (n = 9) and non-invasive (n = 42) S. pyogenes clinical isolates. RESULTS: Emm1 was the most prevalent S. pyogenes emm serotype (n = 11) in this set of clinical isolates, with M1UK being the dominant emm1 genotype (4/5 invasive, 3/6 non-invasive isolates). The assay accurately detected M1UK strains. Whole genome sequencing revealed continued presence of Australian M1UK sub-lineages associated with epidemic scarlet fever-causing S. pyogenes in Asia. CONCLUSIONS: Our study establishes a suitable target for detection of the toxigenic M1UK, and confirms the maintenance of M1UK strains in Queensland, Australia. This assay can be deployed in laboratories and provides a valuable, cost-effective tool to enhance surveillance of the expanding M1UK clone.

The Emergence and Impact of the M1UK Lineage on Invasive Group A Streptococcus Disease in Aotearoa New Zealand.

M1UK is associated with current surges in invasive infection globally, partly due to increased production of superantigen streptococcal pyrogenic exotoxin A. We show that M1UK is now the dominant invasive emm1 lineage in Aotearoa New Zealand and is genomically related to community infections, suggesting that measures that effectively prevent group A Streptococcus pharyngitis in children could reduce invasive disease.

Divergent effects of emm types 1 and 12 on invasive group A streptococcal infections-results of a retrospective cohort study, Germany 2023.

As a potential side effect of the severe acute respiratory syndrome coronavirus type 2 pandemic, invasive group A Streptococcus (iGAS) infections in Europe have increased dramatically in both children and adults in the end of 2022. This epidemiological and molecular study describes the distributions of streptococcal genes encoding the M antigen (emm types) and superantigens in patients with invasive and non-invasive GAS infections. From December 2022 to December 2023, a total of 163 GAS isolates were collected from sterile and non-sterile sites of patients at five hospitals in Germany including two tertiary care centers. Genes encoding M protein and superantigens were determined following the guidelines of CDC Streptococcus laboratory. Patients' characteristics were reviewed retrospectively. Correlations of clinical factors, emm types, and superantigens with rates of invasive infections were analyzed. Of the 163 included GAS cases, 112 (69%) were considered as invasive. In total, 33 different emm types were observed, of which emm1.0 (n = 49; 30%), emm89.0 (n = 15; 9%), and emm12.0 (n = 14; 9%) were most prevalent. In total, 70% of emm1.0 isolates belonged to M1UK lineage. No difference in invasive infections was observed for the M1UK lineage compared with other emm1.0 isolates. However, the emm1.0 type, presence of speA1-3, speG, or speJ, as well as adulthood were significantly associated with invasive infections. In contrast, emm12.0 isolates were significantly less associated with invasive infections. Multivariable analysis confirmed a significant influence of speJ and adulthood on iGAS infections. This study underlines the importance of continuous monitoring of genomic trends and identification of emerging GAS variants. This may aid in delineating pathogenicity factors of Streptococcus pyogenes that propel invasive infections.

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak.

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates. IMPORTANCE: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.

M1UKStreptococcus pyogenes causing community-acquired pneumonia, pleural empyema and streptococcal toxic shock syndrome.

OBJECTIVES: Streptococcus pyogenes causes superficial infections but can also cause deep-seated infections and toxin-mediated diseases. In the present study, phylogenetic and in silico prediction analyses were performed on an antimicrobial resistant M1UKS. pyogenes strain causing severe clinical manifestations during the current surge of invasive group A Streptococcus (iGAS) disease. METHODS: A 40-year-old patient was admitted to the hospital with fever, chest pain and fatigue. Based on the clinical and laboratory findings, a diagnosis of sepsis with disseminated intravascular coagulation, community-acquired pneumonia, pleural empyema and streptococcal toxic shock syndrome was made. Microbial identification was performed by multiplex PCR and conventional culturing. Furthermore, antimicrobial susceptibility testing, whole genome sequencing, phylogenomic analysis and in silico prediction analysis of antimicrobial resistance genes and virulence factors were performed. RESULTS: S. pyogenes isolates were detected in pleural fluid and sputum of the patient. Both isolates belonged to the M1UK lineage of the emm1/ST28 clone, being closely related with an M1UK GAS strain from Australia. They exhibited resistance to erythromycin and clindamycin and susceptibility-increased exposure to levofloxacin and carried genes encoding for protein homologues of antibiotic efflux pumps. Moreover, several virulence factors, and a previously described single-nucleotide polymorphism in the 5' transcriptional leader sequence of the ssrA gene, which enhances expression of SpeA, were detected. CONCLUSIONS: The present antimicrobial-resistant M1UKS. pyogenes strain represents the first report of this emerging lineage associated with such manifestations of iGAS disease.

Detection of toxigenic M1UK lineage group A Streptococcus clones in Taiwan.

BACKGROUND: A new sublineage of emm1 group A Streptococcus (GAS), M1UK, has emerged in Europe, North America, and Australia. Notably, a significant portion of emm1 isolates in Asia, particularly in Hong Kong and mainland China, acquired scarlet fever-associated prophages following the 2011 Hong Kong scarlet fever outbreak. However, the presence of the M1UK sublineage has not yet been detected in Asia. METHODS: This study included 181 GAS isolates (2011-2021). The emm type of these isolates were determined, and 21 emm1 isolates from blood or pleural fluid (2011-2021) and 10 emm1 isolates from throat swabs (2016-2018) underwent analysis. The presence of the scarlet fever-associated prophages and the specific single nucleotide polymorphisms of the M1UK clone were determined by polymerase chain reaction and the genome sequencing. RESULTS: The M1UK lineage strains from throat swab and blood samples were identified. One of the M1UK strain in Taiwan carried the scarlet fever-associated prophage and therefore acquired the ssa, speC, and spd1 toxin repertoire. Nonetheless, the increase of M1UK was not observed until 2021, and there was a reduction in the diversity of emm types in 2020-2021, possibly due to the COVID-19 pandemic restriction policies in Taiwan. CONCLUSIONS: Our results suggested that the M1UK lineage clone has introduced in Taiwan. In Taiwan, the COVID-19 restrictions were officially released in March 2023; therefore, it would be crucial to continuously monitor the M1UK expansion and its related diseases in the post COVID-19 era.

Population of invasive group A streptococci isolates from a German tertiary care center is dominated by the hypertoxigenic virulent M1UK genotype.

PURPOSE: Hypertoxigenic Streptococcus pyogenes emm1 lineage M1UK has recently been associated with upsurges of invasive infections and scarlet fever in several countries, but whole-genome sequencing surveillance data of lineages circulating in Germany is lacking. In this study, we investigated recent iGAS isolates from our laboratory at a German tertiary care center for the presence of the M1UK lineage. METHODS: Whole-genome sequencing was employed to characterize a collection of 47 consecutive non-copy isolates recovered from blood cultures (21) and tissue samples (26) in our laboratory between October 2022 and April 2023. RESULTS: M protein gene (emm) typing distinguished 14 different emm types, with emm1 (17) being the dominant type. Single-nucleotide polymorphism (SNP) analysis confirmed the presence of all 27 SNPs characteristic for the M1UK lineage in 14 of 17 emm1 isolates. CONCLUSION: This study has shown for the first time that M1UK is present in Germany and might constitute a driving force in the observed surge of GAS infections. This observation mirrors developments in the UK and other countries and underscores the importance of WGS surveillance to understand the epidemiology of GAS.

Sustained increase of paediatric invasive Streptococcus pyogenes infections dominated by M1UK and diverse emm12 isolates, Portugal, September 2022 to May 2023.

Since autumn 2022, observed numbers of paediatric invasive group A Streptococcus infections in Portugal (n = 89) were higher than in pre-COVID-19 seasons. Between September 2022 and May 2023, the dominant diagnoses were pneumonia (25/79), mostly with empyema (20/25), and sepsis (22/79). A number of cases required admission to intensive care (27/79) and surgery (35/79), and the case fatality rate was 5.1% (4/79). Genomic sequencing (n = 55) revealed multiple genetic lineages, dominated by the M1UK sublineage (26/55) and more diverse emm12 isolates (12/55).

Expansion of Invasive Group A Streptococcus M1UK Lineage in Active Bacterial Core Surveillance, United States, 2019‒2021.

From 2015-2018 to 2019‒2021, hypertoxigenic M1UK lineage among invasive group A Streptococcus increased in the United States (1.7%, 21/1,230 to 11%, 65/603; p<0.001). M1UK was observed in 9 of 10 states, concentrated in Georgia (n = 41), Tennessee (n = 13), and New York (n = 13). Genomic cluster analysis indicated recent expansions.

Increase of Severe Pulmonary Infections in Adults Caused by M1UK Streptococcus pyogenes, Central Scotland, UK.

We characterized the epidemiology, host-pathogen characteristics, and outcomes of severe adult pulmonary Streptococcus pyogenes infections that coincided with a high community caseload in central Scotland, UK. The pulmonary infections had high illness and death rates and were associated with socioeconomic deprivation, influenza A co-infection, and the M1UK lineage of S. pyogenes.

Emerging Invasive Group A Streptococcus M1UK Lineage Detected by Allele-Specific PCR, England, 20201.

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.