A prospective survey of Streptococcus pyogenes infections in French Brittany from 2009 to 2017: Comprehensive dynamic of new emergent emm genotypes

Abstract

Streptococcus pyogenes or group A Streptococcus (GAS) causes diseases ranging from uncomplicated pharyngitis to life-threatening infections. It has complex epidemiology driven by the diversity, the temporal and geographical fluctuations of the circulating strains. Despite the global burden of GAS diseases, there is currently no available vaccination strategy against GAS infections. This study, based on a longitudinal population survey, aimed to understand the dynamic of GAS emm types and to give leads to better recognition of underlying mechanisms for the emergence of successful clones. From 2009 to 2017, we conducted a systematic culture-based diagnosis of GAS infections in a French Brittany population with a prospective recovery of clinical data. The epidemiological analysis was performed using emm typing combined with the structural and functional cluster-typing system for all the recovered strains. Risk factors for the invasiveness, identified by univariate analysis, were computed in a multiple logistic regression analysis, and the only independent risk factor remaining in the model was the age (OR for the entire range [CI95%] = 6.35 [3.63, 11.10]; p<0.0001). Among the 61 different emm types identified, the most prevalent were emm28 (16%), emm89 (15%), emm1 (14%), and emm4 (8%), which accounted for more than 50% of circulating strains. During the study period, five genotypes identified as emm44, 66, 75, 83, 87 emerged successively and belonged to clusters D4, E2, E3, and E6 that were different from those gathering “Prevalent” emm types (clusters A-C3 to 5, E1 and E4). We previously reported significant genetic modifications for emm44, 66, 83 and 75 types resulting possibly from a short adaptive evolution. Herein we additionally observed that the emergence of a new genotype could occur in a susceptible population having specific risk factors or probably lacking a naturally-acquired cluster-specific immune cross-protection. Among emergent emm types, emm75 and emm87 tend to become prevalent with a stable annual incidence and the risk of a clonal expansion have to be considered.

Increasing Incidence of Invasive Group A Streptococcus Disease, Idaho, USA, 2008–2019

“…emm1 was the most common emm type identified in Idaho and also the most common cause of iGAS nationally during 2008-2019 (1,12,23). The diversity of emm types observed in Idaho was consistent with reports from high-income countries in North America and Europe (28)(29)(30). Although no vaccines targeting GAS are available, the 30-valent M proteinbased strep A vaccine, one of the few vaccines under development in phase 1 or 2 clinical trials, would potentially cover 167/194 (86.1%) emm types from Idaho iGAS cases, and possibly more through crossprotection within emm clusters based on M protein structure (31)(32)(33).…”

“…In the United States, expansion over time of select emm types, including 11, 77, and 92, was linked to increasing prevalence of antimicrobial drug–resistant iGAS infections ( 35 ). Factors that contribute to the emergence of emm types are not well understood but might include genetic changes in bacteria and acquisition of new virulence factors, as well as variations in population immunity ( 30 ). emm59 , which emerged initially in Canada and more recently has been found in the southwestern United States, was the most common emm type in Idaho in 2014; all 5 cases were associated with outbreaks, but emm59 declined during subsequent years ( 19 , 36 ).…”

Integrative Reverse Genetic Analysis Identifies Polymorphisms Contributing to Decreased Antimicrobial Agent Susceptibility in Streptococcus pyogenes

“…As the present study was being readied for submission, while sequencing isolates collected in French Brittany ( 48 ), we unexpectedly discovered a group of five emm81 strains that had a highly divergent pbp2x allele not present in the cohort of 26,465 WGSs. These five strains are clonally related, differing from each other on average by only 28 core SNPs.…”

Design of Broadly Cross-Reactive M Protein–Based Group A Streptococcal Vaccines

“…Subsequent studies revealed that the majority of M proteins could be grouped into sequence-based clusters that were immunologically and functionally related (7). Although there are now >200 different M types of Strep A, which are defined by different N-terminal M protein sequences, there is recent evidence that immunity to Strep A may be a combination of cluster-specific and type-specific M Abs (37,38). An emerging concept is that the N terminus of the M protein is structurally constrained based on the requirement for binding host proteins that promote virulence.…”