Epidemiology Analysis of Streptococcus pyogenes in a Hospital in Southern Taiwan by Use of the Updated emm Cluster Typing System

Abstract

g emm typing is the most widely used molecular typing method for the human pathogen Streptococcus pyogenes (group A streptococcus [GAS]). emm typing is based on a small variable region of the emm gene; however, the emm cluster typing system defines GAS types according to the nearly complete sequence of the emm gene. Therefore, emm cluster typing is considered to provide more information regarding the functional and structural properties of M proteins in different emm types of GAS. In the present study, 677 isolates collected between 1994 and 2008 in a hospital in southern Taiwan were analyzed by the emm cluster typing system. emm clusters A-C4, E1, E6, and A-C3 were the most prevalent emm cluster types and accounted for 67.4% of total isolates. emm clusters A-C4 and E1 were associated with noninvasive diseases, whereas E6 was significantly associated with both invasive and noninvasive manifestations. In addition, emm clusters D4, E2, and E3 were significantly associated with invasive manifestations. Furthermore, we found that the functional properties of M protein, including low fibrinogen-binding and high IgG-binding activities, were correlated significantly with invasive manifestations. In summary, the present study provides updated epidemiological information on GAS emm cluster types in southern Taiwan. S treptococcus pyogenes (group A streptococcus [GAS]) is an important Gram-positive human pathogen, which is responsible for more than 500,000 deaths per year (1). Although there is no vaccine available, several vaccine candidates, especially M proteinbased vaccines, are currently in development (2-5). M protein is a bacterial surface protein and has important roles in GAS pathogenesis (6, 7). These include binding to human fibrinogen, complement regulatory proteins, and immunoglobulins; contributing to resistance to phagocytic cell clearance; and inducing vascular leakage during infection (8-15). M protein-based vaccines are constructed from the hypervariable N-terminal region (26-and 30-valent vaccine) or the conserved C-terminal proportion (J8 vaccine and StreptInCor) of the M protein and were all proven to be effective against GAS infection in animal models (2, 3, 5). In addition, phase I trials with the 30-valent and J8 vaccines are under way in North America and Australia, respectively (16).The variable nucleotide sequence encoding the N-terminal region of the M protein is not only the antigenic target for developing GAS vaccines (17-19) but also the basis for the sequence-based emm typing method (20). emm typing is the most widely used molecular typing approach, and more than 200 different emm types have been reported worldwide (21-23). However, since emm typing is based on a small portion of the emm gene, this typing method provides limited information about the predicted conformational structure or functional domains of the M protein (24). emm pattern typing is another typing method that is based on the presence and arrangement of emm and emm-like genes in the GAS genome (25). emm pattern typing has...

Systematic review and meta-analysis of the prevalence of Strep Aemmclusters in Africa to inform vaccine development

“…This is in accordance with previous reports completed by Sagar (40), Dhanda (41) and Arêas (42), that identified emm types belonging to cluster E6 (emm75, emm81) as the predominant isolates obtained from countries closely relating to the impoverished environments within Africa, India and Brazil respectively. However, when referring to invasive disease, the predominant emm clusters are E3, followed by E6 and D4, which is complimentary to the emm cluster data shown by Chiang-Ni (18).…”

“…Australia, Fiji and New Caledonia illustrated that 70%-84% of clusters from isolates were shared, as opposed to comparison of emm types having only 14%-30% commonality between countries (17). In a third study by Chang-Ni in Taiwan, an analysis of both invasive and non-invasive strains revealed that cluster E6 was associated with both types of infections, while clusters D4, E2 and E3 were responsible for causing invasive isolates in their population (18). Recently, Frost demonstrated that M type-specific and cross-reactive immune responses frequently align with emm clusters, raising new opportunities to design multivalent vaccines with broad coverage (19).…”

emm Types and clusters and macrolide resistance of pediatric group A streptococcal isolates in Central Greece during 2011-2017

“…Among pharyngeal isolates, the seven most frequent emm clusters accounted for 98.5% of the emm typed isolates in this study. Other reports have shown similar results: 96.5% of those collected in a prospective study conducted in Western Greece between 1999 and 2005 [29], authors' unpublished data], 92.8% of 7,040 isolates in the USA [12] and 91.1% in Southern Taiwan [39]. High diversity of emm types has been observed in the Pacific region and other lowincome settings [11,40].…”

Systematic Review and Meta-analysis of the Prevalence of Group A Streptococcal emm Clusters in Africa To Inform Vaccine Development

“…Australia, Fiji, and New Caledonia, illustrated that 70% to 84% of clusters from isolates were shared, as opposed to comparison of emm types having only 14% to 30% commonality between countries ( 15 ). In a third study by Chiang-Ni et al in Taiwan, an analysis of both invasive and noninvasive strains revealed that cluster E6 was associated with both types of infections, while clusters D4, E2, and E3 were responsible for causing invasive isolates in their population ( 16 ). Recently, Frost et al demonstrated that M type-specific and cross-reactive immune responses frequently align with emm clusters, raising new opportunities to design multivalent vaccines with broad coverage ( 17 ).…”